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.

Performance evaluation of the commercial aquafeeds available in the market of Pakistan on Channa marulius (Sole) / Avaliação de desempenho dos alimentos aquáticos comerciais disponíveis no mercado do Paquistão em Channa marulius (Sole)

Abstract 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.

Resumo O presente estudo teve como objetivo determinar o efeito de diferentes níveis de proteína sobre o crescimento, composição corporal, perfil de aminoácidos e sorologia de alevinos de Channa marulius. O experimento foi conduzido em dez happas instalados em tanques de terra, cada um abastecido com 10 peixes, por 90 dias. Quatro alimentos para peixes comerciais com níveis de 25%, 30%, 32% e 40% de proteína bruta (PB) foram dados aos peixes com 3% de seu peso corporal úmido três vezes ao dia. Os resultados do estudo revelaram que maior ganho de peso, taxa de conversão alimentar e taxa de sobrevivência foram observados em 30% de proteína alimentar. Enquanto isso, o conteúdo de umidade foi maior em peixes alimentados com 30% de PB, enquanto a proteína bruta mais alta foi registrada em peixes alimentados com 40% de PB. O menor conteúdo de gordura foi observado em rações com 32% de PB. O perfil de aminoácidos dos peixes revelou melhores resultados na ração com 30% de PB. Proteína total, glicose e globulina também foram maiores em peixes alimentados com ração com 30% de PB, enquanto a albumina foi mais alta com 40% de PB. Conclui-se que a ração com 30% de PB apresentou melhores resultados em termos de crescimento, perfil de aminoácidos e parâmetros sorológicos sem afetar a composição corporal dos peixes.

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

Abstract 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.

Resumo O presente estudo teve como objetivo determinar o efeito de diferentes níveis de proteína sobre o crescimento, composição corporal, perfil de aminoácidos e sorologia de alevinos de Channa marulius. O experimento foi conduzido em dez happas instalados em tanques de terra, cada um abastecido com 10 peixes, por 90 dias. Quatro alimentos para peixes comerciais com níveis de 25%, 30%, 32% e 40% de proteína bruta (PB) foram dados aos peixes com 3% de seu peso corporal úmido três vezes ao dia. Os resultados do estudo revelaram que maior ganho de peso, taxa de conversão alimentar e taxa de sobrevivência foram observados em 30% de proteína alimentar. Enquanto isso, o conteúdo de umidade foi maior em peixes alimentados com 30% de PB, enquanto a proteína bruta mais alta foi registrada em peixes alimentados com 40% de PB. O menor conteúdo de gordura foi observado em rações com 32% de PB. O perfil de aminoácidos dos peixes revelou melhores resultados na ração com 30% de PB. Proteína total, glicose e globulina também foram maiores em peixes alimentados com ração com 30% de PB, enquanto a albumina foi mais alta com 40% de PB. Conclui-se que a ração com 30% de PB apresentou melhores resultados em termos de crescimento, perfil de aminoácidos e parâmetros sorológicos sem afetar a composição corporal dos peixes.

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.

Health-Related Quality of Life and Coping Strategies adopted by COVID-19 survivors: A nationwide cross-sectional study in Bangladesh

This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh. MethodsThis is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QOLBREF) questionnaires were used. The data collection period was from June 2020 to March 2021. ResultsMales 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships; whereas, gender showed only significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed significant correlations with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategy (p<0.001); whereas gender and co-morbidities showed significant correlation with problem focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies (p<0.001). ConclusionSurvivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem focused coping, with emotion focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health associated quality of life and coping strategy during and beyond the Delta pandemic.

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.

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.

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.

Evolving Infection Paradox of SARS-CoV-2: Fitness Costs Virulence?

SARS-CoV-2 is evolved into eight fundamental clades where four (G, GH, GR, and GV) are globally prevalent in 2020. How the featured co-occurring mutations of these clades are linked with viral fitness is the main question here and we thus proposed a hypothetical model using in silico approach to explain the plausible epistatic effects of those mutations on viral replication and transmission. Molecular docking and dynamics analyses showed the higher infectiousness of a spike mutant through more favorable binding of G614 with the elastase-2. RdRp mutation p.P323L significantly increased genome-wide mutations (p<0.0001) since more flexible RdRp (mutated)-NSP8 interaction may accelerate replication. Superior RNA stability and structural variation at NSP3:C241T might impact protein and/or RNA interactions. Another silent 5UTR:C241T mutation might affect translational efficiency and viral packaging. These four G-clade-featured co-occurring mutations might increase viral replication. Sentinel GH-clade ORF3a:p.Q57H constricted ion-channel through inter-transmembrane-domain interaction of cysteine(C81)-histidine(H57) and GR-clade N:p.RG203-204KR would stabilize RNA interaction by a more flexible and hypo-phosphorylated SR-rich region. GV-clade viruses seemingly gained the evolutionary advantage of the confounding factors; nevertheless, N:p.A220V might modulate RNA binding with no phenotypic effect. Our hypothetical model needs further retrospective and prospective studies to understand detailed molecular events featuring the fitness of SARS-CoV-2.

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.

Improvement of Left Ventricular Systolic Function after Percutaneous Coronary Intervention in Diabetic Patients with Non-ST elevated Myocardial Infarction.

Long term mortality is higher in Non-ST-segment elevated myocardial infarction (NSTEMI) patients than STEMI paitents. NSTEMI are a high risk factor for ensuing cardiovascular events in diabetic patients. But, use of drug eluting stents (DES) will further improve outcomes in patients with diabetes suffering early percutaneous coronary intervention (PCI). The aim of the study was to determine the changes in left ventricular (LV) systolic activity after successful PCI in NSTEMI diabetic patients was compared with non-diabetic patients. This comparative clinical study was performed in the Department of Cardiology, University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to June 2018. Thirty (30) diabetic and 34 non-diabetic patients with NSTEMI undergoing percutaneous coronary intervention were included in the study. In all patients PCI with drug eluting stent was performed successfully. Earlier echocardiography (2-Dimensional) was done, at release subsequent PCI and 3 months afterward to evaluate the LV systolic activity and compare to diabetics and non-diabetics at all levels of evaluation to assess the outcome of intervention. At baseline LVEF was rather lower in diabetic group than non-diabetic group patients. In diabetics patients segments with abnormal wall motion (WMA) was higher than non-diabetics patients. While the LVEDD, LVIDd and LVIDs were significantly larger in the earlier group than those in the latter group, the LVESV was no different in both groups. At release from hospital, no significant enhancement was observed in either group following PCI in terms of LVEF, number of segments with WMA, LVIDd and LVIDs. However, both LVEDV and LVESV reduced successfully in both groups with decrease of LVESV being more marked in non-diabetics compared with diabetics (p=0.018). However, 3 months after PCI, LVEF improved (8.4±1.2%) in diabetics and 7.9±1.2% in non diabetics patients but this improvement between two groups was not statically significant (p=0.631). Similarly baseline to 3 months after PCI LVIDs reduces in diabetics patients (5.7±1.9%) and 4.8±1.1% in non diabetics patients but the difference between both groups was not significant (p=0.201). Diabetic patients more frequently required 2 stents (p=0.30), while stent's diameter and length did not differ between the study groups. This study demonstrated that improvement of the parameters of left ventricular systolic function after using of drug eluting stent in NSTEMI diabetic patients was not lower to the non diabetic group under same condition. So, suggestion of PCI with drug eluting stent may be extended in NSTEMI diabetic patient.

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.

Evaluation of dose conformity and coverage of target volume for intensity-modulated radiotherapy of pelvic cancer treatment.

BACKGROUND: Better conformity may help in delivering minimum dose to organs at risk (OARs) and maximum dose to planning target volume (PTV). As per the requirements of modern radiotherapy, 95% isodose should cover the PTV, so conformity indices (CIs) are used for evaluating quality of conformation of treatment plans. AIM: This study aimed to investigate degree of conformity for pelvic patients using intensity-modulated radiotherapy (IMRT) technique. Three formulas of CIs described in literature were analyzed in this study. SETTINGS AND DESIGN: This study was performed to evaluate degree of conformity of 18 patients treated with radiotherapy treatment plan using cumulative dose volume histogram. Effectiveness of different CIs was explored for IMRT plans using 15 MV photon beam. Doses delivered to OAR were also studied. STATISTICAL ANALYSIS USED: CI suggested by the International Commission on Radiation Units and Measurements, radiation CI and CI prescription isodose to target volume (PITV) had mean ± standard deviation values of 1.02 ± 0.018, 0.98 ± 0.017, and 1.63 ± 0.333, respectively. RESULTS AND CONCLUSION: Dose distribution for all patients was highly conformal and clinically acceptable. Values of CI PITV exceeded acceptable value for 27% patients with minor deviation. No statistically significant differences were observed for three CIs reported. Target volume lies between 95% and 107% of prescribed dose which shows ideal target coverage. This simple parameter is advantageous since it is easy to interpret and helped determine quality of treatment plan. This study clearly demonstrated that favorable dose distribution in PTV and OARs is achieved using IMRT technique, and hence, the risk of damage to normal tissues is reduced.

Breakfast quality and cardiometabolic risk profiles in an upper middle-aged German population.

BACKGROUND/OBJECTIVES: Little is known about relation of overall breakfast quality with cardiometabolic risk factors. Therefore, this study aimed to explore sex-specific associations between breakfast quality and cardiometabolic risk profiles in a sample of an upper middle-aged German population. SUBJECTS/METHODS: Cardiometabolic profiles of 339 men and 329 women were cross-sectionally assessed using an overall biomarker score (BScore), glycated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), blood pressure, body mass index (BMI) and waist circumference (WC). Overall breakfast quality was assessed by using (i) an a-priori defined breakfast quality score (BQS) and (ii) data-driven breakfast patterns based on principal component analysis (PCA). Multiple linear regression models for association of breakfast quality with all outcomes were adjusted for all potential confounders including overall diet quality. RESULTS: After adjustment for all potential confounders the BQS was inversely associated with the BScore (regression beta with 95% Confidence Interval: -0.29 (052-0.06)) and HbA1c (-0.12 (-0.21, -0.04)) in men; whereas no such associations were observed in women. Four breakfast (B) patterns were identified: B-processed-food pattern, B-cereal pattern, B-high fat pattern and B-dairy & cereal pattern. The B-processed-food pattern was positively associated with HbA1c (0.09(0.01, 0.18)), BMI (0.16 (0.06, 0.26)), and WC (0.17 (0.8, 0.26)) in men, and BMI (0.13 (0.1, 0.25)) and WC (0.11(0.01.0.22)) in women. The B-cereal pattern was inversely associated with BScore (-0.23 (-0.45, -0.01)) and BMI (-0.11 (-0.20, -0.01)) in men and WC(-0.16 (-0.27, -0.05)) in women. The B-dairy & cereal pattern was also inversely associated with BScore (-0.26 (-0.48, -0.04)) in men but not in women. CONCLUSIONS: The overall breakfast quality was cross-sectionally associated with a healthier cardiometabolic profile, especially in upper-middle age men, independent of overall dietary quality. Such analyses should be supplemented by studies investigating the circadian sequence of food intake and metabolic consequences including hard disease endpoints.

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.

Synchronic inverse seasonal rhythmus of energy density of food intake and sleep quality: a contribution to chrono-nutrition from a Polish adult population.

BACKGROUND/OBJECTIVES: There is evidence which suggests that sleep behavior and dietary intake are interlinked. Thus, we investigated whether a seasonal rhythm in food-energy density exists, and how this relates to quality of sleep. SUBJECTS/METHODS: Two hundred and thirty adult volunteers were investigated across the four seasons. Anthropometrical measurements were obtained and The Pittsburgh Sleep Quality Index was used for an assessment of sleep quality and disturbances. The dietary intake was evaluated using a 24 h dietary recall. Generalized estimating equations were used to estimate seasonal changes in energy density and sleep quality, as well as the association of energy density with sleep quality. All analyses were adjusted for age, sex, education, occupation and shift-work. RESULTS: Mean food energy density was significantly higher in winter as compared with other seasons (P<0.05), although no seasonal variations were observed in macronutrient intake (fat and protein). Overall, the sleep quality was low (score value >5) in all seasons, with the lowest quality occurring in winter and the highest in spring (P<0.05). The components of sleep quality score showed that winter had statistically (P<0.05) poorer subjective sleep quality, sleep latency and sleep disturbances, but lower daytime dysfunction compared with spring and summer. After adjusting for seasonal effects (correlated outcome data) and shift-work, energy density was found to be inversely associated (P<0.0001) with sleep quality. CONCLUSIONS: An inverse association between seasonal fluctuation of food energy density and sleep quality was found with winter time, associated with the intake of higher energy dense food products and the lowest sleep quality.

Initial Clinical Experience With the CyPass Micro-Stent: Safety and Surgical Outcomes of a Novel Supraciliary Microstent.

PURPOSE: To evaluate safety and clinical outcomes of a novel supraciliary device, the CyPass Micro-Stent, for surgical treatment of open-angle glaucoma when implanted in conjunction with cataract surgery. PATIENTS AND METHODS: Subjects (n=142) with open-angle glaucoma and cataract underwent combined phacoemulsification, with intraocular lens insertion, and microstent implantation into the supraciliary space of study eyes (n=167). Two analysis cohorts were prespecified based upon medicated baseline intraocular pressure (IOP): ≥21 mm Hg (cohort 1, n=65) or <21 mm Hg (cohort 2, n=102). Glaucoma medications were discontinued or tapered at surgery, and restarted at investigator discretion. The main postoperative outcome measures were adverse events, IOP changes, and number of IOP-lowering medications. RESULTS: Mean±SD follow-up was 294±121 days. No major intraoperative or postoperative complications occurred. Preoperative baseline mean IOP was 20.2±6.0 mm Hg and mean number of IOP-lowering medications was 2.0±1.1. Cohort 1 showed a 35% decrease in mean IOP and a 49% reduction in mean glaucoma medication usage; cohort 2 demonstrated a 75% reduction in mean medication usage while maintaining mean IOP<21 mm Hg. For all eyes, mean IOP at 12 months was 15.9±3.1 mm Hg (14% reduction from baseline). Early and late postoperative IOP elevation occurred in 1.2% and 1.8% of eyes, respectively. Two subjects developed mild transient hyphema, and none exhibited prolonged inflammation, persistent hypotony, or hypotony maculopathy. CONCLUSIONS: CyPass Micro-Stent implantation, combined with cataract surgery, resulted in minimal complications and reduced IOP and IOP-lowering medication use at 12 months postoperatively.