Vd Values Research Articles

Simultaneous determination of eight analytes of Fuzheng Huayu recipe in beagle dog plasma by UHPLC-Q/exactive Orbitrap HRMS and its application to toxicokinetics.

Fuzheng Huayu recipe (FZHY) is a Chinese patent medicine for the treatment of liver fibrosis. This study aimed to investigate the toxicokinetics of FZHY in beagle dogs after oral administration. Blood samples were collected on days 1, 15 and 28 after oral gavage of FZHY dosages of 400 or 1,200 mg/kg body weight once a day. A UHPLC–Q‐Orbitrap method was developed and validated to simultaneously determine and quantify eight components of FZHY in beagle dog plasma. The times to peak concentration for eight components were18–120 min. The peak concentrations (C max) of amygdalin, genistein, daidzein and 3,4‐dihydroxybenzaldehyde were 1.43–43.50 ng/ml, the areas under the concentration–time curve (AUC(0–t)) were 2.45–6,098.25 ng min/ml, and the apparent volumes of distribution (V d) were 0.05–131.23 × 104 ml/kg. The values of C max of prunasin, schisantherin A, schisandrin A and schisandrin were 7.35–1,450.73 ng/ml, the values of AUC(0–t) were 3,642.30–330,388.65 ng min/ml, and the values of V d were 11.15–1,087.18 × 104 ml/kg. No obvious accumulation of the eight compounds was observed in beagle dogs. The results showed that the method is rapid, accurate and sensitive, and is suitable for detecting the eight analytes of FZHY. This study provides an important basis for the assessment of FZHY safety.

Reassessing the Pediatric Dosing Recommendations for Unfractionated Heparin Using Real-World Data: A Pharmacokinetic-Pharmacodynamic Modeling Approach.

Optimal pediatric dosing of unfractionated heparin (UFH) is challenging because of the paucity of clinical outcome and pharmacokinetic-pharmacodynamic (PK/PD) studies in pediatrics. This study aimed to: (i) develop a PK/PD model for UFH, quantified by anti-factor Xa assay, and the UFH effect, measured by activated partial thromboplastin time (aPTT); and (ii) use simulations to evaluate pediatric UFH infusions for achieving the anti-factor Xa (0.3-0.7IU/mL) therapeutic target. Electronic health record data were retrospectively collected from 633 patients aged <19years admitted to Texas Children's Hospital. The PK/PD model was developed using a 70% (training)/30% (testing) split-sample approach. A 1-compartment PK model with linear elimination adequately described the UFH PK. An allometrically scaled body weight on clearance (CL) and volume of distribution (Vd) with an age-dependent maturation function of extracellular water on Vd were the covariates identified. Comparable with literature, the typical values for CL and Vd were 3.28L/(h·50kg) and 8.83L/50kg, respectively. A linear model adequately described the UFH-aPTT relationship with an estimated slope of 150 seconds/(IU/mL). Simulations of the currently recommended starting infusions (28IU/h/kg for pediatrics <1yearold or 20IU/h/kg for pediatrics >1yearold) showed that the anti-factor Xa therapeutic target was achieved only in 15.3%, 14.6%, 36.9%, and 45.11% of subjects in the age groups of <1year, 1-6years, 6-12years, and 12-19years, respectively. In conclusion, the UFH anti-factor Xa target is not achieved initially, especially in young pediatrics, suggesting the need to optimize UFH dosing to achieve higher therapeutic success.

High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?

Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients' glycemic levels, maintaining stable doses of insulin. Prospective, 12-week clinical trial including 67 T1DM patients, supplemented with high doses of cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day; those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml or presented insulin dose variation during the study were not analyzed. Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = -0.033 (CI 95%: -0.064 to -0.002), r2 = 0.1, p <0.05). Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach.

Visit-to-Visit Blood Pressure Variability Are Associated with an Imbalance between Sympathetic and Parasympathetic Tone in Hypertensive Patients

Greater fluctuations in office blood pressure increase the risk of stroke and blood pressure volatility is an important risk factor for cardiovascular events. Effects of sympathetic and parasympathetic nerve on blood pressure regulation are well known, however, those on visit-to visit variation remains unclear. Aim of this study is to clarify the contribution of sympathetic and parasympathetic balance on blood pressure fluctuation. Methods: We enrolled 23 outpatients with essential hypertension. We measured blood pressure, and pulse rate at clinic 14 times in a row and calculated coefficient of variance (CV) as visit-to-visit variability. The velocity of pupil contraction, miosis (VC) and dilation, mydriasis (VD) was determined from pupillary function test. Results: Systolic blood pressure and diastolic blood pressure were not significantly correlated with VC, VD and VD/VC. Heart rate was not correlated with VC and VD, but significantly correlated with VD/VC. CV of systolic blood pressure, diastolic blood pressure and heart rate were not significantly correlated with VC or VD. Ratio of VD to VC significantly negative correlated with CV of blood pressure, diastolic blood pressure, and heart. Value of VD was significantly correlated with value of VC. Conclusion: Visit-to-visit variability of blood pressure and heart rate is not related with sympathetic or parasympathetic tone independently but augmented by the impaired sympathetic and parasympathetic balance.

Use of optical coherence tomography angiography in assessment in conjunctival vascular architecture in health and pathology

Investigation of the capabilities of anterior segment (AS) optical coherence tomography angiography (OCTA) in evaluation of conjunctival vascular architecture in healthy individuals and in various pathological conditions. The study included 17 healthy volunteers (34 eyes; the control group) and 62 patients (68 eyes) with conjunctival lesions of various nature. All participants underwent AS-OCT and AS-OCTA with assessment of qualitative (vessels pattern, lumen, pathologic tortuosity) and quantitative parameters (vessel density (VD, %) in the lesion area). Mean VD (MVD) and local VD (LVD) were determined, as well as VD in perifocal tissues (PVD). OCTA scans in 8 conjunctival sectors showed mostly radial pattern of the vascular architecture, with vessel lumen remaining the same over their entire visible length. Larger-sized vessels in deeper conjunctival layers were discovered in most cases. The lowest VD value (33.3%) was registered in the superotemporal quadrant, and the highest (38.9%) - in the nasal. Tortuosity of the vessels with course disruption, uneven lumen over the length of the vessels and increase in VD were observed in the area of conjunctival lesions in all cases excluding congenital abnormalities, pingueculae and conjunctival melanocytic intraepithelial neoplasia. The malignant nature of the tumors was indicated by dense vessel distribution and difficulties for visualization of intravascular space, and confirmed by pathohistological analysis. An increase in the number of areas with a lace-like pattern was characteristic for melanomas, with mean VD of more than 50% in the most vascularized areas. AS-OCTA is an informative method for the visualization of vessels in healthy conjunctiva and in conjunctival pathology. Local VD in the lesion area should be measured when the vessels are unevenly distributed.

Vertical Structure of Ice Clouds and Vertical Air Motion from Vertically Pointing Cloud Radar Measurements

The vertical structure of ice clouds and vertical air motion (Vair) were investigated using vertically pointing Ka-band cloud radar. The distributions of reflectivity (Z), Doppler velocity (VD), and spectrum width (SW) were analyzed for three ice cloud types, namely, cirrus, anvil, and stratiform clouds. The radar parameters of the cirrus clouds showed narrower distributions than those of the stratiform and anvil clouds. In the vertical structures, the rapid growth of Z and VD occurred in the layer between 8 and 12 km (roughly a layer of −40 °C to −20 °C) for all ice clouds. The prominent feature in the stratiform clouds was an elongated “S” shape in the VD near 7–7.5 km (at approximately −16 °C to −13 °C) due to a significant decrease in an absolute value of VD. The mean terminal fall velocity (Vt) and Vair in the ice clouds were estimated using pre-determined Vt–Z relationships (Vt = aZb) and the observed VD. Although the cirrus clouds demonstrated wide distributions in coefficients a and exponents b depending on cloud heights, they showed a smaller change in Z and Vt values compared to that of the other cloud types. The anvil clouds had a larger exponent than that of the stratiform clouds, indicating that the ice particle density of anvil clouds increases at a faster rate compared with the density of stratiform clouds for the same Z increment. The significant positive Vair appeared at the top of all ice clouds in range up to 0.5 m s−1, and the anvil clouds showed the deepest layer of upward motion. The stratiform and anvil clouds showed a dramatic increase in vertical air motion in the layer of 6–8 km as shown by the rapid decrease of VD. This likely caused increase of supersaturation above. A periodic positive Vair linked with a significant reduction in VD appeared at the height of 7–8 km (approximately −15 °C) dominantly in the stratiform clouds. This layer exhibited a bi-modal power spectrum produced by pre-existing larger ice particles and newly formed numerous smaller ice particles. This result raised a question on the origins of smaller ice particles such as new nucleation due to increased supersaturation by upward motion below or the seeder-feeder effect. In addition, the retrieved Vair with high-resolution data well represented a Kelvin-Helmholtz wave development.

The heterojunction diode application of mesoporous graphitic carbon nitride (mpg-C3N4)

In this study, morphological properties and Schottky diode application of mpg-C3N4 material were investigated. XRD, SEM and TEM analyzes of this material were performed. When the SEM image is examined, it is seen that mpg-C3N4 particles are coated on the surface homogeneously. The p-Si crystal was used as the base material and mesoporous graphitic carbon nitride material mpg-C3N4 was coated on the crystal with spin coating. Thus, reference and mpg-C3N4/p-Si heterojunctions were fabricated. Using the current-voltage (I–V) measurements of the diode, the ideality factory (n) and barrier height (Φb) values were calculated at the room temperature. These values of Ni/mpg-C3N4/p-Si/Al heterojunction diode were determined as n = 1.25 and Φb = 0.83 eV by the Thermionic Emission (TE) method. Furthermore diode parameters (n, Φb and series resistance (Rs) were determined with Cheung and Norde functions. Also capacity-voltage (C–V) measurements of this device were taken for different frequency values. Using this measurements carrier concentration (Na), barrier heights (Φb), Fermi energy level (Ef) and diffusion potential (Vd) values were determined.

Indirect method for determining the dry deposition velocity of submicron particulate matter on leaves

Plant leaves, as natural receptors of airborne particles, can retain particles onto their surfaces, and absorb gaseous pollutants, thus mitigating air pollution and improving air quality. Dry deposition is considered the main process for particle removal from the atmosphere, and its velocity (Vd) is a crucial parameter for describing the process. Wind tunnels, a conventional approach to determine Vd, are costly and require substantial space, and regular inspections to maintain their systematic integrity. Hence, this study established a simpler and more straightforward method based on relevant research to obtain the submicron particulate matter (aerodynamic diameter ≤1 μm; PM1) Vd on plant leaves. This method involves determining the attenuation pattern of particle concentration in a smog chamber. The Vd values of six tree species (three broadleaved and three coniferous) were obtained through the indirect method. In addition, we determined the Vd of the same tree species with a wind tunnel and compared the values from both methods. Through the paired-samples t-test, it's found that there is no significant difference (sig. = 0.59) between these two methods, which means that the indirect method is feasible to determine Vd. We also compared our results with those from other researches, and we found that the Vd values in our study might be lower because leaves and shoots were used in this research, while branches or seedings were selected in the literature. Overall, when applying such values to predictive models or in concrete studies, researchers must consider factors such as real-time meteorological conditions (humidity, temperature, etc.) and pollutant concentration. The indirect method requires less space and is less costly than the wind tunnel method; therefore, it can easily be used to conduct experiments under controlled conditions, which is helpful for simulating various scenarios.

Towards an experimental approach for measuring the removal of urban air pollutants by green roofs

Green roofs are a promising approach to mitigate air pollution in urban environments, but limited experimental data is yet available. In this study, we developed a laboratory-scale setup to measure the removal nitrogen dioxide (NO2) and ozone (O3) using a variety of common green roof species. Experiments were conducted on detached leaves and whole plants using two chambers (0.6 L and 12 L), visible lighting, NOx/O3 sources and online analyzers. Three species were the best performant (Thymus vulgaris, Sedum sexangulare and Heuchera Americana L.) with deposition velocities (vd) ranging from 1.6 to 4.82 m/h for NO2, and 1.7–5.56 m/h for O3. In both cases, thyme was the most effective plant likely due to its higher stomatal area and the reactivity of its volatile metabolites with O3 leading to several oxidized by-products. Furthermore, NO2 uptake was found to be enhanced by surface water released by leaf transpiration leading to the production of nitrous acid (HONO). Similar values of (vd) were observed (3.84–4.65 m/h) when whole thyme plant was used. The soil was also found to be competitive in removing O3 but less performant in capturing NO2. Using a dry deposition model, we estimated that the three plant species can uptake up to 9 kg/ha/year of NO2 and 13.6 kg/ha/year, which fall in agreement with previously reported modeling data. Our experimental approach can be a rapid tool for screening the depollution performances of green roof species enabling an effective prioritization for deployment in urban environments.

Extension of a gaseous dry deposition algorithm to oxidized volatile organic compounds and hydrogen cyanide for application in chemistry transport models.

The dry deposition process refers to flux loss of an atmospheric pollutant due to uptake of the pollutant by the Earth’s surfaces, including vegetation, underlying soil, and any other surface types. In chemistry transport models (CTMs), the dry deposition flux of a chemical species is typically calculated as the product of its surface layer concentration and its dry deposition velocity (Vd); the latter is a variable that needs to be highly empirically parameterized due to too many meteorological, biological, and chemical factors affecting this process. The gaseous dry deposition scheme of Zhang et al. (2003) parameterizes Vd for 31 inorganic and organic gaseous species. The present study extends the scheme of Zhang et al. (2003) to include an additional 12 oxidized volatile organic compounds (oVOCs) and hydrogen cyanide (HCN), while keeping the original model structure and formulas, to meet the demand of CTMs with increasing complexity. Model parameters for these additional chemical species are empirically chosen based on their physicochemical properties, namely the effective Henry’s law constants and oxidizing capacities. Modeled Vd values are compared against field flux measurements over a mixed forest in the southeastern US during June 2013. The model captures the basic features of the diel cycles of the observed Vd. Modeled Vd values are comparable to the measurements for most of the oVOCs at night. However, modeled Vd values are mostly around 1 cm s−1 during daytime, which is much smaller than the observed daytime maxima of 2–5 cm s−1. Analysis of the individual resistance terms and uptake pathways suggests that flux divergence due to fast atmospheric chemical reactions near the canopy was likely the main cause of the large model–measurement discrepancies during daytime. The extended dry deposition scheme likely provides conservative Vd values for many oVOCs. While higher Vd values and bidirectional fluxes can be simulated by coupling key atmospheric chemical processes into the dry deposition scheme, we suggest that more experimental evidence of high oVOC Vd values at additional sites is required to confirm the broader applicability of the high values studied here. The underlying processes leading to high measured oVOC Vd values require further investigation.

Evaluation of the Macular and Choroidal Perfusion in Healthy Turkish Population Using Optical Coherence Tomography Angiography.

PurposeTo investigate the effect of age- and sex-related differences on macular and choroidal perfusion in healthy Turkish individuals by optical coherence tomography angiography (OCTA).MethodsTwo hundred-eight eyes of 116 healthy Turkish individuals (60 females and 56 males, mean age 40.35 ± 12.64 years) were included in this study. OCTA was performed on a 3 × 3-mm region on the macula. The superficial macula whole-image vessel density (wiVD), foveal VD and parafoveal VD vessel density, foveal avascular zone (FAZ) as well as choriocapillaris flow index (CFI) were quantified.ResultsThe mean vessel density was 53.1% ± 2.8% in superficial macula wiVD, 31.7% ± 6.9% in superficial foveal VD and 55.2% ± 3.4% in superficial parafoveal VD for 3 × 3-mm OCTA images. Analysis of 3 × 3-mm scan has revealed a mean value of FAZ area was 0.313 ± 0.112 mm2. The mean CFI for 3 × 3-mm scan was 1.937 ± 0.059. A significant decrease was observed in the mean values of wiVD, parafoveal VD and CFI with age (p < 0.001, p = 0.001, and p < 0.001, respectively), with average yearly reductions of 0.3%, 0.4% and 0.4%, respectively. However, there was no correlation between age and foveal VD (p > 0.05). The FAZ area has shown an age-dependent annual increment, showing an average of 1.26%. The parafoveal VD and FAZ area were significantly higher in females than males (p = 0.027 and p = 0.015, respectively) while other parameters seemed similar (p > 0.05 for all).ConclusionsOur results suggest that age- and sex-related variations were effective on macular and choroidal perfusion. These normative values obtained using OCTA may be clinically useful to the evaluation of retinal and choroidal disorders.

Association between Diabetic Macular Edema and Capillary Non Perfusion; An Optical Coherence Tomography Angiography Study

Aims: The aim is to use of OCTA to describe the retinal structural damages observed in DME and the relationship between the edema and the capillary non perfusion and to quantify VD and the FAZ area.&#x0D; Study Design: prospective, cross sectional, observational study&#x0D; Place and Duration of Study: University Hospitals in the period between March 2018 to March 2020.&#x0D; Methodology: OCTA images were obtained using the AngioVue (Optovue Inc., CA, USA). For quantitative analysis of the VD and the FAZ area with the help of the manufacturer’s automated software.&#x0D; Results: The study included included 160 eyes of 135 diabetic patients, 61 (45%) females and 74 (55%) males and 20 eyes from 20 age-matched healthy individuals (12 males and 8 females). A significantly worse visual acuity was found in diabetic eyes with CME (mean (x̅) ± SD LogMAR 0.61 ± 0.33), than NPDR eyes without macular edema (0.25 ± 0.19), and controls (Mean ± SD LogMAR 0.02 ± 0.05),the values of VD of the SCP were significantly affected more than the DCP very early in the diabetic course (No DR stage) (P=0.040). Moving one stage more in the disease (mild to moderate NPDR with no edema stage) the deep layer got significantly more affected than the superficial layer (P=0.038). In the more advanced stages of the disease and as the macular edema develop and progress (spongy edema and CME) the two plexuses showed decreased VD values nearly to the same degree with the deep plexus affected slightly more (low VD values) than the superficial plexus&#x0D; Conclusion: Using the OCTA machine with AngioAnalytics parameters (vessel density and non-flow area) aided in the objective quantification of macular perfusion and accurate measurement of the FAZ area in diabetic eyes with and without macular edema. Both parameters were significantly correlated with visual function in treatment-naive diabetic eyes with macular edema.

Left bundle branch pacing compared to left ventricular septal myocardial pacing increases interventricular dyssynchrony but accelerates left ventricular lateral wall depolarization

Nonselective His-bundle pacing (nsHBp), nonselective left bundle branch pacing (nsLBBp), and left ventricular septal myocardial pacing (LVSP) are recognized as physiological pacing techniques. The purpose of this study was to compare differences in ventricular depolarization between these techniques using ultra-high-frequency electrocardiography (UHF-ECG). In patients with bradycardia, nsHBp, nsLBBp (confirmed concomitant left bundle branch [LBB] and myocardial capture), and LVSP (pacing in left ventricular [LV] septal position without proven LBB capture) were performed. Timings of ventricular activations in precordial leads were displayed using UHF-ECG, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. Duration of local depolarization (Vd) was determined as width of the UHF-QRS complex at 50% of its amplitude. In 68 patients, data were collected during nsLBBp (35), LVSP (96), and nsHBp (55). nsLBBp resulted in larger e-DYS than did LVSP and nsHBp [- 24 ms (-28;-19) vs -12 ms (-16;-9) vs 10 ms (7;14), respectively; P <.001]. nsLBBp produced similar values of Vd in leads V5-V8 (36-43 ms vs 38-43 ms; P = NS in all leads) but longer Vd in leads V1-V4 (47-59 ms vs 41-44 ms; P <.05) as nsHBp. LVSP caused prolonged Vd in leads V1-V8 compared to nsHBp and longer Vd in leads V5-V8 compared to nsLBBp (44-51 ms vs 36-43 ms; P <.05) regardless of R-wave peak time in lead V5 or QRS morphology in lead V1 present during LVSP. nslbbp preserves physiological LV depolarization but increases interventricular electrical dyssynchrony. LV lateral wall depolarization during LVSP is prolonged, but interventricular synchrony is preserved.

Optical Coherence Tomography Angiography for the Evaluation of Retinal Vasculature in Fabry Disease: Our Experience and Review of Current Knowledge.

Purpose: Optical coherence tomography angiography (OCTA) is a non-invasive and objective tool for the evaluation of the retinal microvascular changes in Fabry disease (FD). We investigated changes in retinal vasculature in FD patients, and the possible correlation with systemic parameters, by using OCTA, and reviewed the current status of literature.Methods: Thirteen FD patients (eight females, five males, mean age 49.85 ± 14.7 years) were compared with 13 age- and sex-matched healthy controls. OCTA 3 × 3 mm macular scans were performed in all subjects. We evaluated the vessel density and vessel perfusion in distinct macular areas (whole, inner, and outer) of both the superficial capillary plexus (SCP VD and SCP VP) and of the deep capillary plexus (DCP VD and DCP VP). We also evaluated the foveal avascular zone (FAZ) metrics (area, perimeter, and circularity), and correlation between systemic and OCTA parameters. A literature review on the current understanding of OCTA in FD is then presented.Results: FD patients showed significantly lower SCP VD values in the whole area (17.37 ± 2.08 mm−1 vs. 18.54 ± 1.21 mm−1; p-value 0.022), as well as in the outer area (17.46 ± 2.10 mm−1 vs. 19.08 ± 1.14 mm−1; p-value 0.002), but not in the inner. Even the DCP VD was significantly lower in all the imaged areas: whole (17.75 ± 3.93 mm−1 vs. 19.71 ± 1.20 mm−1; p-value 0.024), outer (18.25 ± 4.17 mm−1 vs. 20.33 ± 1.20 mm−1; p-value 0.023), and inner (19.54 ± 4.17 mm−1 vs. 21.96 ± 1.55 mm−1; p-value 0.011). There were no significant differences in vessel perfusion parameters (both SCP VP and DCP VP ones) and FAZ. No significant correlations were found between the OCTA parameters and systemic parameters (maximal left ventricular wall thickness and glomerular filtration rate) in FD patients.Conclusions: OCTA can be considered as a promising non-invasive tool, which enables a quantitative evaluation of retinal vascular involvement in FD, despite the varying data reported in literature. Our results support the use of OCTA as an objective tool to evaluate retinal vascular abnormalities in FD. The utility of OCTA in FD needs to be validated by longitudinal studies taking into account the overall progression of the disease.

Predicting blood-to-plasma concentration ratios of drugs from chemical structures and volumes of distribution in humans

Despite their importance in determining the dosing regimen of drugs in the clinic, only a few studies have investigated methods for predicting blood-to-plasma concentration ratios (Rb). This study established an Rb prediction model incorporating typical human pharmacokinetics (PK) parameters. Experimental Rb values were compiled for 289 compounds, offering reliable predictions by expanding the applicability domain. Notably, it is the largest list of Rb values reported so far. Subsequently, human PK parameters calculated from plasma drug concentrations, including the volume of distribution (Vd), clearance, mean residence time, and plasma protein binding rate, as well as 2702 kinds of molecular descriptors, were used to construct quantitative structure–PK relationship models for Rb. Among the evaluated PK parameters, logVd correlated best with Rb (correlation coefficient of 0.47). Thus, in addition to molecular descriptors selected by XGBoost, logVd was employed to construct the prediction models. Among the analyzed algorithms, artificial neural networks gave the best results. Following optimization using six molecular descriptors and logVd, the model exhibited a correlation coefficient of 0.64 and a root-mean-square error of 0.205, which were superior to those previously reported for other Rb prediction methods. Since Vd values and chemical structures are known for most medications, the Rb prediction model described herein is expected to be valuable in clinical settings.Graphical abstract

A software for quantification of vessel density in glaucoma: An OCT-Angiography study

To assess the capillary vessel density in the peripapillary region of glaucoma patients in comparison to controls using automated software. We performed an observational, cross-sectional case-control study with 72 eyes of glaucoma patients (with strict selection criteria) and 30 age-matched healthy controls. We used an optical coherence tomography angiography device (Triton, Topcon) with scans of 4.5×4.5mm centered on the optic nerve head, excluding images of poor quality. Since this device does not quantify vessel density, we wrote software (with Visual Studio©) that allowed us to remove large blood vessels and quantify the capillary density in the peripapillary region. We tested the ability of OCT-A to differentiate glaucoma from controls using the receiver operating characteristic curve (ROC). We also verified whether VD was correlated with visual field mean deviation. VD was significantly lower in glaucoma than in controls, notably the whole-image VD of 72.45±7.45% in glaucoma and 77.87±3.77% in controls (P<0.001). VD values were correlated with visual fields (Spearman correlation of 0.33; P 0.0017). ROC was moderate (color VD of 0.629±0.143), but better than that of the visual field (0.229±0.077) or the retinal nerve fiber layer thickness assessed by OCT (0.326±0.064). This software is useful for quantifying vessel density at the optic disc, peripapillary and capillary levels and for documenting glaucomatous changes in vascularization. OCT-A might be useful in diagnosis of glaucoma.

Comparative study of retinal nerve fibre layer thickness and retinal peripapillary capillary plexus microvascular vessel density: structure-function relationship analysis in glaucoma.

To investigate whether the retinal peripapillary capillary plexus vessel density (RPCP VD) or the retinal nerve fibre layer thickness (RNFLT) is better in showing the structure-function relationship in glaucoma. Sixty-seven patients with primary open-angle glaucoma (POAG) in one eye and no visual field loss in fellow eye were included in this study. The scans of RPCP VD and RNFLT, and the standard automated perimetry data [including mean deviation (MD), pattern standard deviation (PSD), sector-based pattern deviation (PD) values] were analysed and compared. The global RNFLT was associated with MD (P = 0.035). RNFLTs of the superotemporal, superonasal, inferotemporal and inferonasal quadrants were associated with the corresponding PD (P = 0.004, <0.001, 0.002 and 0.012). The global RPCP VD was found to be associated with MD and PSD (P = 0.030 and 0.049, respectively). RPCP VD of the superotemporal quadrant was associated with PD of the corresponding quadrant, as well as with PSD (P = 0.003 and 0.043, respectively). Remaining RPCP VD values were only associated with the PD values of the corresponding quadrants (P < 0.05). The associations of the RPCP VD with PD were stronger than those of the RNFLT with PD [RPCP VD vs RNFLT: R2 = 0.624 vs 0.558 (P < 0.001 for both) for the superotemporal, 0.649 vs 0.552 for the superonasal (P < 0.001 for both), 0.598 vs 0.427 for the inferotemporal (P < 0.001 for both), 0.581 vs 0.408 for the inferonasal (P < 0.001 for both), 0.594 vs 0.068 (P < 0.001 vs 0.098) for the temporal, and 0.338 vs 0.195 (P < 0.001 vs 0.004) for the nasal quadrants]. In conclusion, the VD of RPCP was more informative in terms of the structure-function relationship in POAG. Future prospective follow-up studies with larger sample sizes are required to confirm the findings.

Convection-Enhanced Arborizing Catheter System Improves Local/Regional Delivery of Infusates Versus a Single-Port Catheter in Ex Vivo Porcine Brain Tissue.

Standard treatment for glioblastoma is noncurative and only partially effective. Convection-enhanced delivery (CED) was developed as an alternative approach for effective loco-regional delivery of drugs via a small catheter inserted into the diseased brain. However, previous CED clinical trials revealed the need for improved catheters for controlled and satisfactory distribution of therapeutics. In this study, the arborizing catheter, consisting of six infusion ports, was compared to a reflux-preventing single-port catheter. Infusions of iohexol at a flow rate of 1 μL/min/microneedle were performed, using the arborizing catheter on one hemisphere and a single-port catheter on the contralateral hemisphere of excised pig brains. The volume dispersed (Vd) of the contrast agent was quantified for each catheter. Vd for the arborizing catheter was significantly higher than for the single-port catheter, 2235.8 ± 569.7 mm3 and 382.2 ± 243.0 mm3, respectively (n = 7). Minimal reflux was observed; however, high Vd values were achieved with the arborizing catheter. With simultaneous infusion using multiple ports of the arborizing catheter, high Vd was achieved at a low infusion rate. Thus, the arborizing catheter promises a highly desirable large volume of distribution of drugs delivered to the brain for the purpose of treating brain tumors.

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance. A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM). A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL. A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.

Hypovitaminosis D in the Greek Elderly Population Doesn't Concern Only Patients with Hip Fracture.

IntroductionVitamin D (VD) deficiency seems to be an underestimated public health issue, especially in countries with a significant duration of sunlight throughout the year, as in this sunny Mediterranean region where this cross-sectional observational study was held. This study was conducted to assess the hypothesis that a higher prevalence of hypovitaminosis D exists in the elderly population with a hip fracture as compared with patients with knee/hip osteoarthritis or lumbar spondylosis in a south-western Mediterranean region.MethodsThis study included 61 consecutive patients with a mean age of 83 years who sustained a hip fracture (Group A). Sixty patients, with an average age of 73 years, who suffered from degenerative hip/knee osteoarthritis or lumbar spondylosis were subsequently selected as the control group (Group B). Parathyroid hormone (PTH) and 25-hydroxy VD blood levels were measured.ResultsNinety-six point seven percent (96.7%; 59/61) of the individuals with hip fracture and 81.7% (49/60) in the controls were found with abnormal VD values (<30 ng/ml). The comparison of vitamin D values between the total samples of group A and B revealed a statistically significant difference (unpaired t-test, p<0.0001) while both male (p=0.0049) and female (p<0.0001) individuals in group A also showed statistically significant lower VD levels than their counterparts did. In addition, increased levels of parathormone were observed in women of group A (p=0.0016) and, therefore, for group A in the total sample (p=0.0004) while no statistical significance was observed in males (p=0.7712). Age was found to be an independent risk factor for VD deficiency in both groups (Group A p=0.04, Group B p=0.043). It is noteworthy that only four patients from group B (6, 67%) and none from group A had undergone blood tests for VD and PTH evaluation before hospital admission.ConclusionsΤhe results confirmed the initial hypothesis of the study. Although VD hypovitaminosis concerns the majority of elderly living in this south-western Mediterranean region, the authors suggest VD and PTH measurements regardless of annual insolation, to identify and counsel the elderly with an increased risk of hip fracture and to avoid perioperative complications in patients who undergo elective orthopedic surgeries.