Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients comorbidly affected by Type 2 diabetes.

The mortality of coronavirus disease 2019 (COVID-19) disease is very high among the elderly or individuals having comorbidities such as obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes the metagenomic features in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients with or without type 2 diabetes, to identify the microbial interactions associated with its fatal consequences.This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2-infected diabetic and nondiabetic patients with controls adjusted for age and gender. The metagenomics based on next-generation sequencing was performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. All three groups possessed significant bacterial diversity and dissimilarity indexes (p < 0.05). Spearman's correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r = 0.6-1.0, p < 0.05), and 109 positive correlations between normal flora and probiotic bacteria (r > 0.6, p < 0.05). The SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and secondary infection-causing bacteria (p < 0.05) with a simultaneous decrease of normal flora (p < 0.05). The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19-infected diabetic patients, although a few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those comorbid patients.

A pharmacokinetic-pharmacodynamic (PKPD) model-based analysis of tedizolid against enterococci using the hollow-fibre infection model.

BACKGROUND: Tedizolid is a novel oxazolidinone antibiotic. Considering the higher antibacterial effect in immunocompetent compared with immunosuppressed animals, it is not recommended in immunocompromised patients. OBJECTIVES: In this study, we assessed the 'pure' pharmacokinetic-pharmacodynamic (PKPD) relationship for tedizolid against Enterococcus in the hollow-fibre infection model (HFIM). METHODS: Unbound plasma concentration time profiles (200-5000 mg/day IV) were simulated in the HFIM over 120 h against an Enterococcus faecalis strain and two clinical isolates of Enterococcus faecium (VRE-vanB and VRE-vanA). Next, a PKPD model describing tedizolid efficacy against bacterial isolates was developed. A population PK model was linked to the developed PKPD model and utilized to predict the bacterial kinetics in plasma and in target tissues [adipose, muscle, epithelial lining fluid (ELF) and sputum] over 120 h of therapy. RESULTS: The PKPD model adequately described the bacterial kill kinetics for all bacterial populations. At the human recommended dose of 200 mg/day, bacterial growth was predicted in plasma and all tissues, except for ELF. Bacteriostasis was observed only at a higher dose of 1200 mg/day over 120 h. An fAUC/MIC of 80 related to stasis over 120 h. Subpopulations resistant to 3 × MIC were amplified in plasma and target tissues, except for ELF, at doses of 200-800 mg/day. CONCLUSIONS: The human dose of 200 mg/day was insufficient to suppress bacterial growth in the HFIM, indicating that further components contribute to the clinical effect of tedizolid. This study supports the warning/precaution for tedizolid to limit its use in immunocompromised patients.

Effects of electric potential, NaCl, pH and distance between electrodes on efficiency of electrolysis in landfill leachate treatment.

This study investigated the effects of different parameters on the removal efficiencies of organic and inorganic pollutants in landfill leachate treatment by electrolysis. Different parameters were considered such as the electric potential (e.g., 24, 40 and 60 V), hydraulic retention time (HRT) (e.g., 40, 60, 80, 100 and 120 min), sodium chloride (NaCl) concentration (e.g., 1, 3, 5 and 7%), pH (e.g., 3, 7 and 9), electrodes materials [e.g., aluminum (Al) and iron (Fe)] and distance between electrodes (e.g., 1, 2 and 3 cm). The best operational condition of electrolysis was then recommended. The electric potential of 60 V with HRT of 120 min at 5% of NaCl solution using Al as anode and Fe as cathode (kept at a distance of 3 cm) was the most efficient condition which increased the removal efficiencies of various parameters such as turbidity, salinity, total suspended solids (TSS), total dissolved solids (TDS), biochemical oxygen demand (BOD), chemical oxygen demand (COD) and heavy metals (e.g., Zn and Mn). The higher removal percentages of many parameters, especially COD (94%) and Mn (93%) indicated that the electrolysis is an efficient technique for multi-pollutants (e.g., organic, inorganic and heavy metals) removal from the landfill leachate.

Performance of select color-difference formulas in the blue region.

The main objective of this work was to test the performance of major formulas for assessment of small suprathreshold color differences in the blue region. The models examined include CIELAB color space based equations, including CIELAB, CIE94, CIEDE2000, CMC (l:c), BFD (l:c), and formulas based on more uniform color spaces, such as DIN99d, CAM02-SCD, CAM02-UCS, OSA-GP, and OSA-Eu in comparison against data obtained via visual assessments. For this purpose, a dataset around the CIE high-chroma blue color center, hereafter called NCSU-B2, was developed. The NCSU-B2 dataset comprised 65 textile substrates and a standard, with a mean ΔE(ab)* color difference of 2.72, ranging from 0.54-5.72. Samples were visually assessed by 26 subjects against the reference gray scale in three separate trials with at least 24 h between assessments. A total of 5070 assessments were obtained. The standardized residual sum of squares (STRESS) index was used to examine the performance of various formulas for this dataset, as well as a previously developed NCSU-B1 low-chroma blue dataset [Color Res. Appl. 36, 27, 2011], and blue centers from other established visual datasets. Results show that formulas based on more recent uniform color spaces provide better agreement with perceptual data compared with models based on CIELAB space.

Human embryonic stem cell differentiation into odontoblastic lineage: an in vitro study.

AIM: The aim of this study was to differentiate human embryonic stem cells (hESCs) into odontoblastic lineage in an optimized culture milieu. METHODOLOGY: In Phase 1, hESCs were differentiated into mesenchymal stem cells (H9-MSCs). In Phase 2, H9-MSCs were then differentiated into odontoblast-like cells (H9-Odont) under the stimulation of FGF-8 and BMP-4. Alternatively, H9-MSCs were differentiated into osteogenic lineage (H9-Osteo). In Phase 3, H9-Odont were seeded on 17% EDTA-treated dentine substrates in the presence of FGF-8 and BMP-4 for further differentiation. All experiments were performed in triplicate (n = 3). One-way anova was used to test hESC differentiation into different cell types. Post hoc Tukey's test was used to compare between groups. P < 0.05 was considered statistically significant. RESULTS: H9-Odont expressed the odontoblastic marker DSPP gene 125.47 ± 0.1 (SD)-folds higher compared with H9-MSCs at mRNA level (real-time RT-PCR). Additionally, the flow cytometry results revealed 53.1 ± 3.4 (SD) % of DSP (+) cells in H9-Odont. Alternatively, H9-Osteo expressed 5.9 ± 2.2 (SD) % of DSP (+) cells. Moreover, the SEM results demonstrated that H9-Odont were found to undergo morphological changes from a fibroblast-like shape into more rounded shapes with cytoplasmic extensions into the dentinal tubules when seeded on 17% EDTA-treated dentine substrate in the presence of FGF-8 and BMP-4. However, H9-Osteo and H9-MSCs did not show similar morphological changes under similar culture milieu. CONCLUSION: This study supports the potential of hESCs as a stable, consistent, unlimited and 'off-the-shelf' cell source to obtain odontoblastic cells for future clinical and research applications.

Biotissue stent for supraciliary outflow in open-angle glaucoma patients: surgical procedure and first clinical results of an aqueous drainage biostent.

BACKGROUND/AIMS: To report a first-in-human trial in open-angle glaucoma (OAG) subjects treated with a new microinterventional biostent-reinforced cyclodialysis technique to enhance supraciliary aqueous drainage. METHODS: Subjects (N=10; 74.1±7.9 years old) with OAG and cataracts underwent combined phacoemulsification cataract surgery with implantation of a permanent endoscleral supraciliary biostent to reinforce a controlled cyclodialysis cleft. The biostent comprised decellularised scleral allograft tissue microtrephined into a polymer tubular implant intraoperative/postoperative safety, intraocular pressure (IOP) and glaucoma medications were tracked through 12 months postimplantation. RESULTS: Baseline medicated IOP averaged 24.2±6.9 mm Hg with subjects using 1.3±0.8 IOP-lowering medications. Successful biostent implantation was achieved in all individuals without significant complications. Immediate IOP lowering was sustained through 1 year. Twelve-month mean IOP was reduced 40% from baseline to 14.6±3.2 mm Hg (p=0.004; paired two-tailed t-test), and 80% of patients achieved >20% IOP reduction. Biostenting reduced glaucoma medication use 62%, from a baseline mean of 1.3 required medications to 0.5 medications (p=0.037) at postoperative 12 months. The biotissue implant was well tolerated and demonstrated good endothelial safety with only 11% endothelial cell loss at 12 months after combined phaco-biostenting surgery, similar to that expected after phacoemulsification alone. Mean BCVA increased from baseline 20/130 Snellen to 20/36 at postoperative 12 months (p=0.001). CONCLUSION: Supraciliary biostenting in OAG patients is well tolerated, has a good safety profile and produces long-term IOP-lowering while reducing glaucoma medication requirements.

Democratizing Health Care in the Metaverse: How Video Games can Monitor Eye Conditions Using the Vision Performance Index: A Pilot Study.

Objective: In a world where digital media is deeply engrained into our everyday lives, there lies an opportunity to leverage interactions with technology for health and wellness. The Vision Performance Index (VPI) leverages natural human-technology interaction to evaluate visual function using visual, cognitive, and motor psychometric data over 5 domains: field of view, accuracy, multitracking, endurance, and detection. The purpose of this study was to describe a novel method of evaluating holistic visual function through video game-derived VPI score data in patients with specific ocular pathology. Design: Prospective comparative analysis. Participants: Patients with dry eye, glaucoma, cataract, diabetic retinopathy (DR), age-related macular degeneration, and healthy individuals. Methods: The Vizzario Inc software development kit was integrated into 2 video game applications, Balloon Pop and Picture Perfect, which allowed for generation of VPI scores. Study participants were instructed to play rounds of each video game, from which a VPI score was compiled. Main Outcome Measures: The primary outcome was VPI overall score in each comparison group. Vision Performance Index component, subcomponent scores, and psychophysical inputs were also compared. Results: Vision Performance Index scores were generated from 93 patients with macular degeneration (n = 10), cataract (n = 10), DR (n = 15), dry eye (n = 15), glaucoma (n = 16), and no ocular disease (n = 27). The VPI overall score was not significantly different across comparison groups. The VPI subcomponent "reaction accuracy" score was significantly greater in DR patients (106 ± 13.2) versus controls (96.9 ± 11.5), P = 0.0220. The VPI subcomponent "color detection" score was significantly lower in patients with DR (96.8 ± 2.5; p=0.0217) and glaucoma (98.5 ± 6.3; P = 0.0093) compared with controls (101 ± 11). Psychophysical measures were statistically significantly different from controls: proportion correct (lower in DR, age-related macular degeneration), contrast errors (higher in cataract, DR), and saturation errors (higher in dry eye). Conclusions: Vision Performance Index scores can be generated from interactions of an ocular disease population with video games. The VPI may offer utility in monitoring select ocular diseases through evaluation of subcomponent and psychophysical input scores; however, future larger-scale studies must evaluate the validity of this tool. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

The effect of proanthocyanidins on the bond strength and durability of resin sealer to root dentine.

AIM: To investigate the effect of proanthocyanidins (PAs)-rich grape seed extract on the biodegradation resistance of demineralized root dentine and on the bond strength and durability between resin-based sealer and root dentine. METHODOLOGY: Single-rooted premolars (n = 28) were divided into PAs-treated and nontreated specimens. Root canals were instrumented to apical size 40, filled with RealSeal SE sealer/Core, sectioned into slices of 1 mm thickness from middle and coronal thirds and stored for 1 week or 3 months in distilled water. Specimens were subjected to push-out strength testing with the load applied perpendicularly in an apical to coronal direction using a universal testing machine. Remaining apical thirds were viewed by scanning electron microscopy after 3-months storage. Additional root canals were filled with rhodamine-B-labelled sealer and viewed by confocal laser scanning microscopy. Unfilled roots (n = 6) were sliced, demineralized, PAs-treated or left untreated and exposed to 24 h collagenase to determine hydroxyproline release in the supernatant. Two-way anova was used to test the effect of both dentine treatment with PAs and anatomical locations on bond strength and hydroxyproline release. Tukey-Kramer multiple comparison post hoc test was used to compare between groups. RESULTS: No difference in bond strength was found after 1-week storage between both PAs-treated (crosslinked) and untreated (noncrosslinked) groups in the coronal thirds. However, treatment with PAs revealed higher 1-week bond strength values (P ≤ 0.05) in the middle thirds. Generally, 3-month storage decreased the bond strength compared to 1-week within each of the crosslinked and noncrosslinked groups. However, the decrease in the bond strength after 3 months was less for the crosslinked specimens compared to the noncrosslinked specimens. Confocal images revealed a relatively uniform fluorescent interfacial layer and tubular penetration after 1 week in both groups. SEM images revealed more intact resin sealer/dentine interfaces with PAs crosslinking after 3 months. In addition, hydroxyproline release was significantly less (P ≤ 0.05) with crosslinked specimens. CONCLUSION: Treating root dentine with PAs-rich grape seed extracts improved the biodegradation resistance of demineralized root dentine and enhanced the bond strength and durability between resin-based sealer and root dentine after short-term water storage.

Growth Performance, Carcass Traits and Serum Mineral Chemistry as Affected by Dietary Sodium and Sodium Salts Fed to Broiler Chickens Reared under Phase Feeding System.

A basal diet (0.8 g/kg dNa) was formulated in which each of the two sources (NaHCO3 and Na2SO4) were supplemented in such a way to attain four levels (1.7, 2.6, 3.5, and 4.4 g/kg) of total dNa, respectively, under 4×2 factorial arrangement. Eight dietary treatments were replicated four times, with 40 birds in each replicate (n = 1,280). The diets supplemented with Na2SO4 to attain higher levels of dNa showed highest BW gain and feed intake (FI) during d 1 to 10 (interaction effects) while 2.6 g/kg dNa exhibited improved BW gain and gain:feed (FG) during d 11 to 20. Linear rise in daily water intake (DWI) was associated with diets containing increasing dNa during d 1 to 42 (p≤0.036). During the first 10 d, DWI:FI was found highest in NaHCO3 diets while Na2SO4 diets showed highest DWI:FI during last 10 d of the experiment (p≤0.036). Increasing dNa and changing Na2SO4 with NaHCO3 salt increased pH and resulted in poor growth performance. Dressing weight (p≤0.001) and abdominal fat (p≤0.001; quadratic effect) were reduced, whereas breast (p≤0.001) and thigh (p<0.001) weights were aggravated with increasing dNa (linear effects). Present findings suggested higher levels of dNa from Na2SO4 as the supplemental salt in broiler diets would produce better growth performance, especially in first ten days of life, and improve carcass and body organ characteristics.

Effect of cardiopulmonary bypass on tissue injury markers and endothelial activation during coronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass grafting (CABG) is done either using cardiopulmonary bypass (CPB) or without using CPB (OPCAB). But, recently, reports have shown that CPB is associated with increased postoperative morbidity because of the involvement of many systems. AIMS: The aim of this prospective study was to evaluate the influence of the technique of surgery on various tissue injury markers and the extent of endothelial activation in patients undergoing CABG and OPCAB coronary revascularization. SETTINGS AND DESIGN: This study was conducted at a tertiary healthcare center during the period May 2008 to December 2009. MATERIALS AND METHODS: This was a prospective nonrandomized blinded study. The activities of Creatine Phosphokinase (CK) and its isoenzyme CK-MB, Lactate dehydrogenase (LDH), levels of cardiac Troponin I, soluble vascular cell adhesion molecule-1 (sVCAM-I) and systemic nitric oxide production were assessed. STATISTICAL ANALYSIS: All the results were expressed as Mean ± SD. P value ≤ 0.05 was considered significant. The statistical analysis was carried out using SPSS Version 11.5-computer software (SPSS Inc., Chicago, IL, USA). RESULTS: The surgical trauma had elevated CK, CK-MB and Troponin I in both the groups and further elevation was seen in the CABG group in comparison to OPCAB (P<0.001). The Troponin I concentrations showed an increase from 0.11 ± 0.02 preoperatively to 6.59 ± 0.59 (ng/ml) at 24 h (P<0.001) compared to the OPCAB group. Mean serum levels of sVCAM-1 increased significantly after surgery in both the groups (P<0.02). To determine serum nitric oxide (NO) production, NO2- and NO3- (stable end products of NO oxidation) were analyzed which also increased significantly at 24 h in both the groups. But the increase was not significant at 48 h in both the groups compared to the preoperative value in our study. CONCLUSION: The present study indicates that, despite comparable surgical trauma, the OPCAB significantly reduces tissue injury. The overall pattern of endothelial activation after OPCAB is significantly lower than that after CABG. This may contribute to improved organ function, and improved postoperative recovery.

Investigation of Power Specific Motor Primitives in an Upper Limb Rotational Motion.

The purpose of this study was to investigate muscle synergies (MS) during upper limb cycling motion across power levels (20, 40, 60, 80, 100, and 120 watts). The MS hypothesis is important to the understanding of modular control for human movements. In this study, we explore its importance in execution of phasic movements at various power levels. Electromyographic (EMG) signals were recorded from 7 upper limb muscles during cycling for 30s on a hand-cycle ergometer. A Non-Negative Matrix factorization (NNMF) algorithm was used to extract MS. Cosine similarity was used to compare the MS and cross-correlation was used to compare activation coefficients. We found that the number and structure of synergies were consistent across power levels while admitting modulation in their activation coefficients. A total of three shared MS explaining ≥95% of the variance accounted for (VAF) represented push and pull mechanism during cyclic motion.

Two-year outcomes of the MINIject drainage system for uncontrolled glaucoma from the STAR-I first-in-human trial.

BACKGROUND/AIMS: The current study evaluates the efficacy and safety of the stand-alone implantation of the MINIject (iSTAR Medical, Wavre, Belgium) supraciliary, microinvasive glaucoma drainage device in patients with medically uncontrolled open-angle glaucoma. METHODS: This prospective, multicentre, first-in-human, single-arm interventional study evaluated stand-alone, ab interno implantation in 25 patients of a 5 mm long uveoscleral device made of STAR biocompatible material, which is a soft, microporous, flexible silicone. The primary outcome was the reduction of intraocular pressure (IOP) at 6 months compared with baseline, and follow-up continued until 2 years for 21 patients. Secondary outcomes included success defined as diurnal IOP of ≤21 mmHg and >5 mmHg with an IOP reduction of 20% without (complete) or with/without (qualified) glaucoma medication. RESULTS: Mean baseline IOP was 23.2±2.9 mmHg on 2.0±1.1 glaucoma medication ingredients and decreased to 13.8±3.5 mmHg (-40.7% reduction) on 1.0±1.3 medications 2 years after implantation. Complete success was achieved in 47.6% of patients (10/21) and qualified success in 100% of patients (21/21) at the 2-year follow-up. All patients achieved a 20% IOP reduction with 48% of patients medication-free. No serious ocular adverse events or additional glaucoma surgery were reported. Mean central endothelial cell density (ECD) mildly decreased from 2411 cells/mm2 (n=26) to 2341 cells/mm2 (n=21) at 24 months, which represents a 5% decrease for matched eyes. No patient had a ≥30% decrease in central ECD. CONCLUSION: This first-in-human study on the stand-alone implantation of the MINIject supraciliary drainage system shows promising IOP-lowering results and medication reduction over 24 months with few adverse events. TRIAL REGISTRATION NUMBER: NCT03193736.

Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules.

Microtubule-associated protein tau becomes abnormally hyperphosphorylated in Alzheimer's disease (AD) and accumulates as tangles of paired helical filaments in neurons undergoing degeneration. We now show that in solution normal tau associates with the AD hyperphosphorylated tau (AD P-tau) in a nonsaturable fashion, forming large tangles of filaments 3.3 +/- 0.7 nm in diameter. These tangles, which are not detected in identically treated normal tau or AD P-tau alone, are made up of filaments several microns in length and are labeled with tau antibodies. Dephosphorylation with alkaline phosphatase abolishes the ability of AD P-tau to aggregate with normal tau and prevents tangle formation. AD P-tau disassembles microtubules assembled from normal tau and tubulin. These data provide insight into how the hyperphosphorylation of tau might lead to the formation of the neurofibrillary tangles and the degeneration of the affected neurons in AD.

Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the presence of numerous neurons with neurofibrillary tangles of paired helical filaments (PHFs). The microtubule-associated protein tau in abnormally hyperphosphorylated form is the major protein subunit of the PHF. We now show that PHF tangles isolated from AD brains are glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles by endoglycosidase F/N-glycosidase F converts them into bundles of straight filaments 2.5 +/- 0.5 nm in diameter, similar to those generated by the interaction of normal tau and abnormally hyperphosphorylated tau (AD P-tau). Deglycosylation plus dephosphorylation, but not deglycosylation alone, of AD P-tau and tau from PHF tangles restores their microtubule polymerization activity. Dephosphorylation of deglycosylated PHF tangles results in increased tau release. Thus, although the abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation appears to be responsible for the maintenance of the PHF structure.

Role of oral clonidine on intraopereative haemodynamic stability for craniotomies of intracranial space occupying lesion.

This was an analytical comparative study. Aim of this study was to observe the effect of oral clonidine on intra operative haemodynamic stability in intracranial space occupying lesion (ICSOL) patients who underwent craniotomy. Total 60 patients were distributed into case and control group. Number of cases was 30 in each study group of this study. Mean age of experimental and control were significantly close to each other. Baseline weight, pulse, systolic blood pressure, diastolic blood pressure and mean pressure also showed a significant similarity between each group. Variable of each group was collected during different events of craniotomy. All variable of pulse, systolic blood pressure, diastolic blood pressure and mean pressure were tabulated by line chart and fluctuation of variable was measured by significance test. The fluctuation of mean pressure was respectively 11.6%, 11.2%, 12.4%, 11.4%, 14.2%, 15.6%, 10% and 9.4% in different events of craniotomy in hemodynamically unstable group and it was respectively 11.1%, 10.9%, 10.4%, 9.9%, 9.2%, 9.4%, 8.6% and 8.7% in hemodynamically stable group. 'P' value was less than 0.05. It was observed that fluctuation of haemodynamic parameters were significantly less in experimental group where oral clonidine was used as premedication.

Performance evaluation of the commercial aquafeeds available in the market of Pakistan on Channa marulius (Sole).

The present study aimed to determine the effect of different levels of protein on the growth, body composition, amino acid profile and serology of Channa marulius fingerlings. The experiment was conducted in ten happas installed in earthen ponds, each stocked with 10 fishes for 90 days. Four commercial fish feeds having 25%, 30%, 32% and 40% crude protein (CP) levels were fed to fish at 3% of their wet body weight three times a day. The results of the study revealed that highest weight gain, feed conversion ratio and survival rate were observed in 30% protein feed. Meanwhile, moisture content was higher in fish fed with 30% CP feed while highest crude protein was recorded in 40% CP fed fish. Lowest fat content was observed in 32% CP feed. Amino acid profile of fish revealed better results in 30% CP feed. Total protein, glucose and globulin were also highest in fish feeding 30% CP feed, while albumin was highest in 40% CP feed. It is concluded that 30% CP feed showed better results in terms of growth, amino acid profile and serological parameters without effecting fish body composition.

Predicting changes in cataract surgery health outcomes using a cataract surgery appropriateness and prioritization instrument.

OBJECTIVE: Determine whether items in a cataract surgery appropriateness and prioritization questionnaire can predict change in best corrected visual acuity (BCVA) and health related quality of life (HRQOL) following cataract surgery. METHODS: 313 patients with a cataract in Ontario, Canada were recruited to participate. BCVA was measured using the Snellen chart. HRQOL was measured using a generic instrument (EQ5D), a visual functioning instrument (Catquest-9SF), and an appropriateness and prioritization instrument (17 items). Outcomes were measured preoperatively and 3-6 months postoperatively. Descriptive statistics were used to describe demographics and outcomes. For each appropriateness and prioritization questionnaire item, a one-way ANOVA was used to compare group means of the change in BCVA, EQ5D, and Catquest-9SF. RESULTS: Participants had a mean age of 69 years and were 56% female. BCVA improved in 81%, EQ5D in 49.6%, and Catquest-9SF score in 84% of patients. Improvement in both BCVA and Catquest-9SF scores were found in 68.5% of patients. The ANOVA showed a statistically significant association between a change in BCVA and the ability to participate in social life, and a statistically significant association between a change in Catquest-9SF and glare, extent of impairment in visual function, safety and injury concerns, ability to work and care for dependents, ability to take care of local errands, ability to assist others and ability to participate in social life. CONCLUSIONS: Almost all patients had improved BCVA and/or visual functioning after surgery. Seven variables from the cataract appropriateness and prioritization instrument were found to be predictors of improvement in Catquest-9SF measuring visual functioning.

Biomedical soft robots: current status and perspective.

This paper reviews the current status of soft robots in biomedical field. Soft robots are made of materials that have comparable modulus of elasticity to that of biological systems. Several advantages of soft robots over rigid robots are safe human interaction, ease of adaptation with wearable electronics and simpler gripping. We review design factors of soft robots including modeling, controls, actuation, fabrication and application, as well as their limitations and future work. For modeling, we survey kinematic, multibody and numerical finite element methods. Finite element methods are better suited for the analysis of soft robots, since they can accurately model nonlinearities in geometry and materials. However, their real-time integration with controls is challenging. We categorize the controls of soft robots as model-based and model-free. Model-free controllers do not rely on an explicit analytical or numerical model of the soft robot to perform actuation. Actuation is the ability to exert a force using actuators such as shape memory alloys, fluid gels, elastomers and piezoelectrics. Nonlinear geometry and materials of soft robots restrict using conventional rigid body controls. The fabrication techniques used for soft robots differ significantly from that of rigid robots. We survey a wide range of techniques used for fabrication of soft robots from simple molding to more advanced additive manufacturing methods such as 3D printing. We discuss the applications and limitations of biomedical soft robots covering aspects such as functionality, ease of use and cost. The paper concludes with the future discoveries in the emerging field of soft robots.

A pharmacometric approach to define target site-specific breakpoints for bacterial killing and resistance suppression integrating microdialysis, time-kill curves and heteroresistance data: a case study with moxifloxacin.

OBJECTIVES: Pharmacokinetic-pharmacodynamic (PK-PD) considerations are at the heart of defining susceptibility breakpoints for antibiotic therapy. However, current approaches follow a fragmented workflow. The aim of this study was to develop an integrative pharmacometric approach to define MIC-based breakpoints for killing and suppression of resistance development for plasma and tissue sites, integrating clinical microdialysis data as well as in vitro time-kill curves and heteroresistance information, exemplified by moxifloxacin against Staphylococcus aureus and Escherichia coli. METHODS: Plasma and target site samples were collected from ten patients receiving 400 mg moxifloxacin/day. In vitro time-kill studies with three S. aureus and two E. coli strains were performed and resistant subpopulations were quantified. Using these data, a hybrid physiologically based (PB) PK model and a PK-PD model were developed, and utilized to predict site-specific breakpoints. RESULTS: For both bacterial species, the predicted MIC breakpoint for stasis at 400 mg/day was 0.25 mg/L. Less reliable killing was predicted for E. coli in subcutaneous tissues where the breakpoint was 0.125 mg/L. The breakpoint for resistance suppression was 0.06 mg/L. Notably, amplification of resistant subpopulations was highest at the clinical breakpoint of 0.25 mg/L. High-dose moxifloxacin (800 mg/day) increased all breakpoints by one MIC tier. CONCLUSIONS: An efficient pharmacometric approach to define susceptibility breakpoints was developed; this has the potential to streamline the process of breakpoint determination. Thereby, the approach provided additional insight into target site PK-PD and resistance development for moxifloxacin. Application of the approach to further drugs is warranted.