## Τετάρτη, 17 Απριλίου 2019

### Applied Physiology

Regional differences in facial skin blood flow responses to thermal stimulation

### Purpose

The facial skin blood flow (SkBF) shows regional differences in the responses to a given stimulation. The facial SkBFs, especially in the eyelid and nose exhibit unique response to physiological and psychological stimuli, but the mechanisms inducing those regional differences remain unclear. To investigate whether the regional differences in the local control of vasomotion in facial vessels correspond to the regional differences in facial SkBF response, we monitored the relative change of facial SkBF to regional thermal stimulation. We hypothesized that heat stimulation dilates the cutaneous vessels in the eyelid, while cold stimulation constricts those in the nose, which was based on previous findings

### Methods:

A thermal stimulator was used to apply temperature increase (from 20 to 40 °C at 2 °C/min) and decrease (from 40 to 20 °C at 2°C/min) in a randomized order to the right eyelid, nose, right cheek, and forehead of 14 healthy young males. The facial SkBF was measured for 10 s using laser-speckle flowgraphy when temperatures of 20 °C, 30 °C, and 40 °C had been applied for 30 s in both trials.

### Results

The SkBF in the eyelid did not change significantly during any thermal stimulation, and the nasal SkBF did not decrease significantly during cold stimulation. The SkBFs in the cheek and forehead increased significantly with the applied temperature.

### Conclusions

These findings indicate that a large regional variation exists in facial skin blood flow response to local heating or cooling and that the regional variation did not correspond to the unique SkBF responses in the previous studies.

The effect of severe and moderate hypoxia on exercise at a fixed level of perceived exertion

### Purpose

The purpose of this study was to determine the primary cues regulating perceived effort and exercise performance using a fixed-RPE protocol in severe and moderate hypoxia.

### Methods

Eight male participants (26 ± 6 years, 76.3 ± 8.6 kg, 178.5 ± 3.6 cm, 51.4 ± 8.0 mL kg− 1 min− 1 $$\dot {V}$$ O2max) completed three exercise trials in environmental conditions of severe hypoxia (FIO2 0.114), moderate hypoxia (FIO2 0.152), and normoxia (FIO2 0.202). They were instructed to continually adjust their power output to maintain a perceived effort (RPE) of 16, exercising until power output declined to 80% of the peak 30-s power output achieved.

### Results

Exercise time was reduced (severe hypoxia 428 ± 210 s; moderate hypoxia 1044 ± 384 s; normoxia 1550 ± 590 s) according to a reduction in FIO2 (P < 0.05). The rate of oxygen desaturation during the first 3 min of exercise was accelerated in severe hypoxia (− 5.3 ± 2.8% min− 1) relative to moderate hypoxia (− 2.5 ± 1.0% min− 1) and normoxia (− 0.7 ± 0.3% min− 1). Muscle tissue oxygenation did not differ between conditions (P > 0.05). Minute ventilation increased at a faster rate according to a decrease in FIO2 (severe hypoxia 27.6 ± 6.6; moderate hypoxia 21.8 ± 3.9; normoxia 17.3 ± 3.9 L min− 1). Moderate-to-strong correlations were identified between breathing frequency (r = − 0.718, P < 0.001), blood oxygen saturation (r = 0.611, P = 0.002), and exercise performance.

### Conclusions

The primary cues for determining perceived effort relate to progressive arterial hypoxemia and increases in ventilation.

A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction

### Background

Helium in oxygen (HELIOX) can relieve airway obstruction and lower the work of breathing because it increases the threshold at which turbulent gas flow is induced. Less turbulent and more laminar flow lowers the work of breathing. According to guidelines, the fraction of Helium in HELIOX should be maximized (e.g. to 79%). Here, we investigate whether HELIOX with less than 60% of Helium is able to relieve the sensation of dyspnea in healthy volunteers.

### Methods

44 volunteers underwent resistive loading breathing different gases (medical air and HELIOX with a fraction of 25%, 50% or 75% helium in oxygen) in a double-blinded crossover design. Subjects rated their degree of dyspnea (primary outcome parameter) and the variability of noninvasively measured systolic blood pressure was assessed.

### Results

Dyspnea was significantly reduced by HELIOX-containing mixtures with a fraction of helium of 25% or more. Similarly, blood pressure variability was reduced significantly even with helium 25% during respiratory loading with the higher load, whereas with the smaller load an effect could only be obtained with the highest helium fraction of 75%.

### Conclusion

In this clinical trial, HELIOX with less than 60% of helium in oxygen decreased the sensation of dyspnea and blood pressure variability, a surrogate parameter for airway obstruction. Therefore, higher oxygen fractions might be applied without losing the helium-related benefits for the treatment of upper airway obstruction.

### Trial registration

Registration with clinical trials (NCT00788788) and EMA (EudraCT number: 2006-005289-37).

Damage protective effects conferred by low-intensity eccentric contractions on arm, leg and trunk muscles

### Purpose

Low-intensity eccentric contractions with a load corresponding to 10% of maximal voluntary isometric contraction strength (10% EC) attenuate muscle damage in a subsequent bout of higher-intensity eccentric contractions performed within 2 weeks for the elbow flexors, knee flexors and knee extensors. However, it is not known whether this strategy could be applied to other muscles. This study investigated whether 10% EC would confer damage protective effect on high-intensity eccentric contractions (80% EC) for nine different muscle groups.

### Methods

Untrained young men were placed to an experimental or a control group (n = 12/group). Experimental group performed 50 eccentric contractions with a load corresponding to 10% EC at 2 days prior to 50 eccentric contractions with 80% EC for the elbow flexors and extensors, pectoralis, knee flexors and extensors, plantar flexors, latissimus, abdominis and erector spinae. Control group performed 80% EC without 10% EC. Changes in maximal voluntary isometric contraction strength (MVC) and muscle soreness, plasma creatine kinase (CK) activity and myoglobin concentration after 80% EC were compared between groups by a mixed-factor ANOVA.

### Results

MVC recovered faster (e.g., 6–31% greater MVC at 5 days post-exercise), and peak muscle soreness was 36–54% lower for Experimental than Control group for the nine muscles (P < 0.05). Increases in plasma CK activity and myoglobin concentration were smaller for Experimental (e.g., peak CK: 2763 ± 3459 IU/L) than Control group (120,360 ± 50,158 IU/L).

### Conclusions

These results showed that 10% EC was effective for attenuating the magnitude of muscle damage after 80% EC for all muscles, although the magnitude of the protective effect differed among the muscles.

Characterization of torque generating properties of ankle plantar flexor muscles in ambulant adults with cerebral palsy

### Purpose

Weakness of plantar flexor muscles is related to reduced push-off and forward propulsion during gait in persons with cerebral palsy (CP). It has not been clarified to what an extent altered muscle contractile properties contribute to this muscle weakness. Here, we investigated the torque generating capacity and muscle fascicle length in the triceps surae muscle throughout ankle range of motion (ROM) in adults with CP using maximal single muscle twitches elicited by electrical nerve stimulation and ultrasonography.

### Methods

Fourteen adults with CP (age 36, SD 10.6, GMFCS I–III) and 17 neurological intact (NI) adults (age 36, SD 4.5) participated. Plantar flexor torque during supramaximal stimulation of the tibial nerve was recorded in a dynamometer at 8 ankle angles throughout ROM. Medial gastrocnemius (MG) fascicle length was tracked using ultrasonography.

### Results

Adults with CP showed reduced plantar flexor torque and fascicle shortening during supramaximal stimulation throughout ROM. The largest torque generation was observed at the ankle joint position where the largest shortening of MG fascicles was observed in both groups. This was at a more plantarflexed position in the CP group.

### Conclusion

Reduced torque and fascicle shortening during supramaximal stimulation of the tibial nerve indicate impaired contractile properties of plantar flexor muscles in adults with CP. Maximal torque was observed at a more plantarflexed position in adults with CP indicating an altered torque-fascicle length/ankle angle relation. The findings suggest that gait rehabilitation in adults with CP may require special focus on improvement of muscle contractility.

Muscle quality as a complementary prognostic tool in conjunction with sarcopenia assessment in younger and older individuals

### Purpose

This pilot study investigated differences in lean tissue mass, muscle strength, muscle quality (strength per unit of muscle mass; MQ), and functional performance in healthy younger and older individuals. The most robust predictors of appendicular lean mass (ALM) were then determined in each group.

### Methods

Fifty younger (18–45 years) and 50 older (60–80 years) participants completed tests of upper and lower body strength alongside body composition by dual-energy X-ray absorptiometry from which upper- and lower-body MQ were estimated. Available cut-points for older people were used to determine low upper-body MQ in both groups. Low lower-body MQ was determined as at least two standard deviations below the mean of the younger group. Functional performance was assessed by gait speed. Sarcopenia was identified using two established definitions.

### Results

Upper and lower body strength, ALM, lower-body MQ and gait speed were significantly higher in the younger group (all p < 0.002). Sarcopenia was identified in 2–4% of the older group. Low upper-body MQ was evident in 32% and 42% of the younger and older group, respectively. Low lower-body MQ was observed in 4% of younger participants, and 50% of older participants. In both groups, the most robust predictors of ALM were upper and lower body strength (young R2 = 0.74, 0.82; older R2 = 0.68, 0.72).

### Conclusions

Low MQ despite low prevalence rates of sarcopenia in both groups suggests a need for age-specific MQ cut-points. Muscle quality assessments might be useful complementary prognostic tools alongside existing sarcopenia definitions.

Neuromuscular adaptations to wide-pulse high-frequency neuromuscular electrical stimulation training

### Purpose

No studies have evaluated the potential benefits of wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) despite it being an interesting alternative to conventional NMES. Hence, this study evaluated neuromuscular adaptations induced by 3 weeks of WPHF NMES.

### Methods

Ten young healthy individuals (training group) completed nine sessions of WPHF NMES training spread over 3 weeks, whereas seven individuals (control group) only performed the first and last sessions. Plantar flexor neuromuscular function (maximal voluntary contraction (MVC) force, voluntary activation level, H reflex, V wave, contractile properties) was evaluated before the first and last training sessions. Each training session consisted of ten 20-s WPHF NMES contractions (pulse duration: 1 ms, stimulation frequency: 100 Hz) interspaced by 40 s of recovery and delivered at an intensity set to initially evoke ~ 5% of MVC force. The averaged mean evoked forces produced during the ten WPHF NMES-evoked contractions of a given session as well as the sum of the ten contractions force time integral (total FTI) were computed.

### Results

Total FTI (+ 118 ± 98%) and averaged mean evoked forces (+ 96 ± 91%) increased following the 3-week intervention (p < 0.05); no changes were observed in the control group. The intervention did not induce any change (p > 0.05) in parameters used to characterize plantar flexor neuromuscular function.

### Conclusion

Three weeks of WPHF NMES increased electrically evoked forces but induced no other changes in plantar flexor neuromuscular properties. Before introducing WPHF NMES clinically, optimal training program characteristics (such as frequency, duration and intensity) remain to be identified.

High-intensity interval exercise promotes post-exercise hypotension of greater magnitude compared to moderate-intensity continuous exercise

### Purpose

Physical exercise is associated with reduced blood pressure (BP). Moderate-intensity continuous exercise (MCE) promotes post-exercise hypotension (PEH), which is highly recommended to hypertensive patients. However, recent studies with high-intensity interval exercise (HIIE) have shown significant results in cardiovascular disease. Thus, this study aimed to analyze PEH in hypertensive subjects submitted to HIIE and compare it to post MCE hypotension.

### Methods

20 hypertensive adults (51 ± 8 years), treated with antihypertensive medications, were submitted to two different exercise protocols and a control session. The MCE was performed at 60–70% of VO2 reserve, while HIIE was composed of five bouts of 3 min at 85–95% VO2 reserve with 2 min at 50% of VO2 reserve. The following variables were evaluated during exercise, pre- and post-session: clinical BP, heart rate (HR), double product, perception of effort, body mass, height and body mass index.

### Results

Systolic BP decreased after exercise in both sessions, showing greater decrease after HIIE (− 7 ± 10 and − 11 ± 12 mmHg, after MCE and HIIE, respectively, p ≤ 0.01). Diastolic BP also decreased after both sessions, but there were no significant differences between the two sessions (− 4 ± 8 and − 7 ± 8 mmHg, after MCE and HIIE, respectively).

### Conclusion

Both exercise sessions produced PEH, but HIIE generated a greater magnitude of hypotension. The HIIE protocol performed in this study caused a greater cardiovascular stress during exercise; however, it was safe for the studied population and efficient for reducing BP after exercise.

Effects of the trunk position on muscle stiffness that reflects elongation of the lumbar erector spinae and multifidus muscles: an ultrasonic shear wave elastography study

### Purpose

The present study aimed to clarify the effects of the trunk position on muscle stiffness that reflects elongation of the lumbar erector spinae and lumbar multifidus muscles using ultrasonic shear wave elastography (SWE).

### Methods

The study included ten healthy men. The shear elastic modulus of the left lumbar erector spinae and lumbar multifidus muscles were evaluated using ultrasonic SWE. Measurement postures for the left lumbar erector spinae muscle were (1) prone position (Rest), (2) sitting position with the trunk flexed (Flexion), (3) the Flexion position adding right trunk lateral flexion (Flexion-Lateral Flexion), and (4) the Flexion position adding right trunk rotation (Flexion-Rotation 1). The left lumbar multifidus muscle were measured in positions (1)–(3), and (5) the Flexion position adding left trunk rotation (Flexion-Rotation 2).

### Results

The shear elastic modulus of the lumbar erector spinae muscle in the Flexion-Lateral Flexion position was significantly higher than that in the Rest, Flexion, or Flexion-Rotation 1 positions. Shear elastic modulus of the lumbar multifidus muscle was similar in the Flexion, Flexion-Lateral Flexion, and Flexion-Rotation 2 positions, but significantly lower in the Rest position.

### Conclusions

The results of the present study suggest that the lumbar erector spinae muscle is stretched effectively in the position adding trunk contralateral lateral flexion to flexion. The results also indicate that the lumbar multifidus muscle, which does not appear to be affected by adding trunk contralateral lateral flexion or ipsilateral rotation to flexion, is stretched effectively in the trunk flexion position.

Suitability of jumps as a form of high-intensity interval training: effect of rest duration on oxygen uptake, heart rate and blood lactate

### Purpose

High-intensity interval training (HIT) has been shown to be an effective endurance training method. However, most HIT research has been conducted on running and cycling. The aim of this study was to assess the suitability of intermittent exercises such as jumps as a type of HIT.

### Methods

Respiratory gases, heart rate and ground reaction forces were recorded for 21 participants (age 25 ± 4 years, mass 73 ± 12 kg, 13 male) during 5 distinct jump sessions on different days that varied with respect to the rest durations in between series (0, 15 or 30 s) and in between jumps (0, 1 or 2 s). Blood lactate was determined 3 min after the last series. Prior to the first session, maximal jump height as well as V′O2max during cycling was recorded.

### Results

Peak oxygen uptake and heart rate were nearly maximal during all five jump sessions (87–99% of V′O2max, 96–98% of maximal heart rate). The time spent at more than 90% of V′O2max (1–43% of the total session duration), average jump height (34–82% of maximal jump height) and lactate accumulation (4–9 mmol/l) differed between jump sessions, mainly depending on the rest interval between jumps (p < 0.001, rmANOVA between sessions with different rest intervals between jumps).

### Conclusion

With short rest intervals, jumping elicited comparable acute responses as reported for running or cycling HIT. Thus, training programs using intermittent exercises should elicit similar adaptations as other forms of HIT, provided the rest intervals are sufficiently short. Heart rate might be of limited value when comparing different types of HIT.

### Environmental Science and Pollution Research

Remediation of cobalt-polluted soil after application of selected substances and using oat ( Avena sativa L.)

### Abstract

The aim of the study was to determine the effectiveness of soil application of manure, clay, charcoal, zeolite, and calcium oxide in remediation of soil polluted with cobalt (0, 20, 40, 80, 160, 320 mg Co kg−1 of soil). The following were determined: weight of harvested plants as well as the content of cobalt in grain, straw, and roots of oat. In addition, tolerance index (Ti), cobalt bioconcentration (BCF), translocation (TF), and transfer (TFr) coefficients were derived. In the series without amendments, the increasing doses of cobalt had a significant effect by decreasing the yields of oat grain and straw and the mass of its roots. Also, lower tolerance index values were noted in the objects polluted with cobalt, especially with its highest dose. The application of manure had the strongest effect on increasing the mass of particular organs of the test plant, while the application of charcoal led to a significant decrease in this respect. The application of all substances to the soil, and especially manure and calcium oxide, resulted in higher tolerance index Ti values. The growing contamination of soil with cobalt caused a significant increase in the content of this element in oat and in the values of the translocation coefficient, in contrast to the effects noted with respect to the bioconcentration and transfer coefficients. All the substances applied to soil reduced the content of cobalt and its bioconcentration in oat straw, in opposition to grain and roots, limited its translocation, but elevated the transfer of this element from soil to plants. Soil contamination with cobalt promoted the accumulation of lead and copper in grain, cadmium, lead, nickel, zinc, manganese, and iron in straw, as well as cadmium, nickel, zinc, and manganese in oat roots. As the cobalt dose increased, the content of other trace elements in oat organs either decreased or did not show any unambiguous changes. Of all the tested substances, the strongest influence on the content of trace elements was produced by calcium oxide in straw and roots and by zeolite in roots, whereas the weakest effect was generated by manure in oat grain. Oat is not the best plant for phytoremediation of soils contaminated with cobalt.

### Abstract

Radiolytic oxidation of 2,4-dichlorophenol (2,4-DClP) in aqueous solutions demonstrated that ·OH predominantly adds to the unsubstituted positions of the aromatic ring and that elimination of chloride at the 4 position is important because the –OH group enhances the electron density at this position, which is favorable for the electrophilic reactions. The total yield obtained was 0.540 μmol/J. Radiation-induced degradation of 2,4-DClP was conducted in oxygen-free aqueous solutions (0.1, 0.25, 0.50, and 0.7 mmol/dm3), saturated with N2O, and aerated and under irradiation at low and high doses. The results demonstrate that the largest degradation occurred in oxygen-free solutions due to oxidation (·OH) and reduction reactions (H· and $${\mathrm{e}}_{\mathrm{aq}}^{-}$$ ) and attack of the $${\mathrm{e}}_{\mathrm{aq}}^{-}$$ at the ipso position of –Cl, producing HCl. The degradation was affected to a large extent by the concentration and to a lesser extent by the presence or absence of oxygen in which the 2,4-DClP solution was irradiated. At concentrations less than 1 mmol/dm3, 2,4-DClP was degraded in the solution at an absorbed dose level of 1 kGy. At higher doses, the product concentrations increased to up to 30% of the dose required for the total degradation of 2,4-DClP; then, they decreased. A graph plotting the logarithm of the relative concentration as a function of the dose shows a linear correlation, which indicates that the radiolytic degradation followed pseudo-first-order reaction kinetics. The oxidation was followed by the chemical oxygen demand (COD). COD decreases when the solute concentration increases. This fact has a dependence on the presence or absence of oxygen too.

Setting-up a Real-Time Air Quality Forecasting system for Serbia: a WRF-Chem feasibility study with different horizontal resolutions and emission inventories

### Abstract

In this paper, the influence of the horizontal model grid size and anthropogenic gridded emissions on the air quality forecast in Serbia was analyzed using the online-coupled Weather Research and Forecasting model with Chemistry (WRF-Chem). For that purpose, six simulations were performed. The model horizontal grid size was 20 × 20 km, 10 × 10 km, and 5 × 5 km. Two anthropogenic gridded emission inventories with different grid sizes were used, the global RETRO (REanalysis of the TROpospheric chemical composition) and the EMEP (The European Monitoring and Evaluation Program) for each model horizontal grid size. The modeled O3, NO2, and PM10 concentrations in all six simulations were compared with the measured hourly data at the Serbian Environmental Protection Agency (SEPA) stations and an EMEP station during August 2016. The analysis shows that the influence of the model grid size is larger on PM10 than on the O3 and NO2 concentration. The concentration of O3 and PM10 has a similar dependence on the emissions and the model grid size, while NO2 has a larger dependence on the emission than on the model grid size. The simulation with the 5 × 5 km grid size and the EMEP anthropogenic emissions has optimal performance compared with the measured concentration. In this optimal simulation, the modeled O3 concentrations overestimated the measured values at 3 stations and underestimated the measured values at 2 stations. At most stations, the modeled NO2 concentrations underestimated the measured values. The modeled PM10 concentrations highly underestimated the measured values at all stations.

Air pollution survey across the western Mediterranean Sea: overview on oxygenated volatile hydrocarbons (OVOCs) and other gaseous pollutants

### Abstract

Despite the Mediterranean Sea basin is among the most sensitive areas over the world for climate change and air quality issues, it still remains less studied than the oceanic regions. The domain investigated by the research ship Minerva Uno cruise in Summer 2015 was the Tyrrhenian Sea. An overview on the marine boundary layer (MBL) concentration levels of carbonyl compounds, ozone (O3), and sulfur dioxide (SO2) is reported. The north-western Tyrrhenian Sea samples showed a statistically significant difference in acetone and SO2 concentrations when compared to the south-eastern ones. Acetone and SO2 values were higher in the southern part of the basin; presumably, a blend of natural (including volcanism) and anthropogenic (shipping) sources caused this difference. The mean acetone concentration reached 5.4 μg/m3; formaldehyde and acetaldehyde means were equal to 1.1 μg/m3 and 0.38 μg/m3, respectively. Maximums of 3.0 μg/m3 for formaldehyde and 1.0 μg/m3 for acetaldehyde were detected along the route from Civitavecchia to Fiumicino. These two compounds were also present at levels above the average in proximity of petrol-refining plants on the coast; in fact, formaldehyde reached 1.56 μg/m3 and 1.60 μg/m3, respectively, near Milazzo and Augusta harbors; meanwhile, acetaldehyde was as high as 0.75 μg/m3 at both sites. The levels of formaldehyde agreed with previously reported measurements over Mediterranean Sea and elsewhere; besides, a day/night trend was observed, confirming the importance of photochemical formation for this pollutant. According to this study, Mediterranean Sea basin, which is a closed sea, was confirmed to suffer a high anthropic pressure impacting with diffuse emissions, while natural contribution to pollution could come from volcanic activity, particularly in the south-eastern Tyrrhenian Sea region.

Sewage waste water application improves the productivity of diverse wheat ( Triticum aestivum L.) cultivars on a sandy loam soil

### Abstract

Water stress due to climate change is an emerging threat to wheat (Triticum aestivum L.) productivity in the arid regions of the world which will impact the future food security. In this scenario, the investigations are needed to check the feasibility of alternate sources of irrigation water to fulfill the irrigation demands of the crops in the arid regions. This 2-year study was aimed to investigate the influence of three irrigation sources (sewage water, canal water, and underground water) on the productivity of 10 wheat cultivars under an arid climate of Layyah, Pakistan. The results indicated that the number of fertile tillers, grains per spike, 1000-grain weight, and grain yield varied from 114 to 168 m−2, 34.8 to 53.3, 33.4 to 38.4 g, and 2.68 to 4.05 Mg ha−1, respectively in various wheat cultivars. The highest fertile tillers (168 m−2) were recorded in cultivar Gold-2016 followed by Aas-2011 (155 cm), AARI-2011 (153 m−2), and Ujala-2016 (150 m−2). The highest 1000-grain weight of 38.4 g was recorded in cultivar NARC-2016. The grains per spike (53.3) were the highest in cultivar Ujala-2016. The grain yields were the highest in cultivars Ujala-2016 (4.05 Mg ha−1) and Gold-2016 (3.91 Mg ha−1). The highest grain yield of 3.71 Mg ha−1 was recorded with sewage water irrigation against the grain yield of 3.18 and 2.91 Mg ha−1 in canal and underground water irrigation, respectively. There existed a strong co-relation of fertile tillers and grains per spike with the grain yield of wheat. Application of sewage water also enhanced the total nitrogen, extractable potassium, and available phosphorous in soil. In crux, the cultivation of recently bread wheat cultivars (viz. Ujala-2016, Gold-2016) and the irrigation of field with sewage water in the absence of canal water might be a viable option to boost wheat productivity under arid regions. A range of genetic variability existed for different traits in the cultivars; therefore, these can be used to breed wheat cultivars to be used for sewage water cultivation.

Production and characterization of bio-mix fuel produced from the mixture of raw oil feedstock, and its effects on performance and emission analysis in DICI diesel engine

### Abstract

Bio-mix is a fuel derived from the raw mixture of different non-edible oils to enhance the saturation level. In this study, raw oil mixture was transesterified to form bio-mix methyl ester (BMME). Fuel properties of BMME was measured and results showed that saturated fatty acids (SFA), cetane number (CN), and oxidation stability (OS) were increased, whereas density, viscosity, HHV, flash point, iodine number, and acid number were decreased for BMME as compared to individual biodiesels. Brake specific energy consumption (BSEC) of BMME was higher than diesel fuel but similar to individual biodiesel, while brake thermal efficiency (BTE) was lower than diesel fuel but higher than the individual biodiesel. (NOx) and CO2 emission of BMME was found lower (approximately 20%); meanwhile, smoke opacity and CO emission biodiesel increased compared to diesel fuel, whereas (HC) emission of BMME was lower at low load condition but it is increased at high load. Bio-mix fuel could be the good replacement of diesel fuel.

Comparison and optimization of different methods for Microcystis aeruginosa 's harvesting and the role of zeta potential on its efficiency

### Abstract

This study has compared the harvesting efficiency of four flocculation methods, namely, induced by pH, FeCl3, AlCl3 and chitosan. No changes were observed on M. aeruginosa cells. Flocculation assays performed at pH 3 and 4 have shown the best harvesting efficiency among the pH-induced tests, reaching values above 90% after 8 h. The adjustment of zeta potential (ZP) to values comprised between − 6.7 and − 20.7 mV enhanced significantly the settling rates using flocculant agents, being FeCl3 the best example where increments up to 88% of harvesting efficiency were obtained. Although all the four methods tested have presented harvesting efficiencies above 91% within the first 8 h after the optimization process, the highest performance was obtained using 3.75 mg L−1 of FeCl3, which allowed reaching 92% in 4 h.

Aminosilane-grafted spherical cellulose nanocrystal aerogel with high CO 2 adsorption capacity

### Abstract

In this study, the cellulose nanocrystals (CNC) obtained by acid hydrolysis of microcrystalline cellulose (MCC) are customized by suspension to obtain a spherical CNC hydrogel. The N-(2-aminoethyl) (3-amino-propyl) methyldimethoxyansile (AEAPMDS) preparation was grafted to spherical CNC hydrogel using a water phase heat treatment. Finally, aerogel samples were obtained by tert-butanol replacement and freeze-drying. The test results confirmed that the aminosilane was grafted on CNC. Electron micrographs and N2 sorption isotherms showed that the pores of the aerogel were partially blocked due to the introduction of AEAPMDS, and the specific surface area was decreased. Due to the presence of chemisorption, the amount of CO2 adsorbed at a pressure of 3 bar by the modified aerogel (2.63 mmol/g) was greatly improved compared with the unmodified aerogel (0.26 mmol/g), and the adsorption results were fit well by the Langmuir model. Thus, our experiments provided the opportunity to develop a new CO2 absorbent material.

How production-based and consumption-based emissions accounting systems change climate policy analysis: the case of CO 2 convergence

### Abstract

Much of the existing research analyses on emissions and climate policy are dominantly based on emissions data provided by production-based accounting (PBA) system. However, PBA provides an incomplete picture of driving forces behind these emission changes and impact of global trade on emissions, simply by neglecting the environmental impacts of consumption. To remedy this problem, several studies propose to consider national emissions calculated by consumption-based accounting (CBA) systems in greenhouse gas (GHG) assessments for progress and comparisons among the countries. In this article, we question the relevance of PBA's dominance. To this end, we, firstly, try to assess and compare PBA with CBA adopted in greenhouse gas emissions accounting systems in climate change debates on several issues and to discuss the policy implications of the choice of approach. Secondly, we investigate the convergence patterns in production-based and consumption-based emissions in 35 Annex B countries for the period between 1990 and 2015. This study, for the first time, puts all these arguments together and discusses possible outcomes of convergence analysis by employing both the production- and consumption-based CO2 per capita emissions data. The empirical results found some important conclusions which challenge most of the existing CO2 convergence studies.

Toxicological effects of toxic metals (cadmium and mercury) on blood and the thyroid gland and pharmacological intervention by vitamin C in rabbits

### Abstract

Cadmium and mercury are non-biodegradable toxic metals that may cause many detrimental effects to the thyroid gland and blood. Vitamin C has been found to be a significant chain-breaking antioxidant and enzyme co-factor against metal toxicity and thus make them less available for animals. The current study was performed to find the effect of individual metals (cadmium and mercury), their co-administration, and the ameliorative effects of vitamin C on some of the parameters that indicate oxidative stress and thyroid dysfunction. Cadmium chloride (1.5 mg/kg), mercuric chloride (1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1. control; 2. Vit C; 3. CdCl2; 4. HgCl2; 5. Vit C + CdCl2; 6. Vit C + HgCl2; 7. CdCl2 + HgCl2, and 8. Vit C + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. triidothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and triglycerides were measured using commercially available kits. The results exhibited significant decline (p < 0.05) in mean hemoglobin, corpuscular hemoglobin, packed cell volume, T3 (0.4 ± 0.0 ng/ml), and T4 (26.3 ± 1.6 ng/ml) concentration. While, TSH (0.23 ± 0.01 nmol/l) and triglyceride (4.42 ± 0.18 nmol/l) were significantly (p < 0.05) increased but chemo-treatment with Vit C reduces the effects of Cd, Hg, and their co-administration but not regained the values similar to those of controls. This indicates that Vit C had a shielding effect on the possible metal toxicity. The Cd and Hg also found to accumulate in vital organs when measured by atomic absorption spectrophotometer. The metal concentration trend was observed as follows: kidney > liver > heart > lungs. It was concluded that Cd and Hg are toxic and tended to bioaccumulate in different organs and their toxic action can be subdued by vitamin C in biological systems.

### Philosophy

Denotation as Complex and Chronologically Extended: anvitābhidhāna in Śālikanātha's  Vākyārthamātṛkā - I

### Abstract

The two theories of verbal cognition, namely abhihitānvaya and anvitābhidhāna, first put forth by the Bhāṭṭa and Prābhākara Mīmāṃsakas respectively in the second half of the first millennium C.E., can be considered as being foundational as all subsequent thinkers of the Sanskritic intellectual tradition (philosophers as well as ālaṃkārikas) engaged with and elaborated upon these while debating the nature of language and meaning. In this paper, I focus on the first chapter (pariccheda) of Śālikanātha's Vākyārthamātṛkā and outline the process of anvitābhidhāna described therein. Śālikanātha explains this as comprising three steps, and thereafter discusses each of these three to elaborate upon and philosophically defend this conception of how one cognizes sentential meaning. The aim of this paper is to present Śālikanātha's three-step model, and thus demonstrate especially the distinct conception of abhidhāna (denotation) for the Prābhākara Mīmāṃsakas (particularly Śālikanātha) as complex and chronologically extended as contrasted with the Bhāṭṭa conception of abhidhāna as non-complex and instantaneous. Such an understanding of the disparate semantic contents with which the Bhāṭṭas and Prābhākaras use the identical term abhidhāna is crucial for any correct study of their respective doctrines.

Aśvaghoṣa's Apologia: Brahmanical Ideology and Female Allure

### Abstract

The question I pose in this paper is simple but crucial: Why did Aśvaghoṣa present Brahmanism as the backdrop for the emergence of Buddhism? In both his epic poems, he presents Brahmanism as the obvious and natural condition of society and kings, in the same way that it is depicted in the Brahmanical writings themselves. It has become increasingly clear that Brahmanical texts present ideologically motivated programs for social engineering rather than accurate descriptions of social reality. If social reality did not obligate Aśvaghoṣa to adopt this posture, then why did Aśvaghoṣa buy into this ideological position of Brahmanism? Why did he not describe the social reality underlying Buddhism in a way similar to Aśoka? While attempting to explore these questions, I will analyze Aśvaghoṣa's arguments against some central theological positions of Brahmanism: First, there is the theological argument that a person must turn to asceticism only after he has raised a family and performed his other religious obligations spelt out in the trivarga and the āśrama system. Second, there is the issue of kāma, both within the trivarga and within the common conception of a householder's life. The paper will attempt to analyze the way Aśvaghoṣa in his two epic poems deals with these two areas, one more strictly theological and the other dealing with themes of sex, eroticism, and conjugal love, all of which present obstacles to the Buddhist path of liberation that runs through the celibate monastery.

After the Unsilence of the Birds: Remembering Aśvaghoṣa's Sundarī

### Abstract

Once encountered in Beautiful Nanda, Aśvaghoṣa's Sundarī is unforgettable. It is easy, then, to forget that we are given to see and hear her only in two of the eighteen chapters of Aśvaghoṣa's long, lyrical narrative of Nanda. When she is given to speak, her words and voice resonate powerfully, but the narrative reduces her at last to silence. Among the last images of her, there is the moment when she is likened to a screaming bird, bereaved of her mate, her voice transformed and eventually drowned out (Beautiful Nanda 6.30). This essay argues for a new interpretation of the salience of this figurative transformation, and of two different ways in which Sundarī is lost to view as she is forgotten or overlooked by characters in the narrative. Along with a close-reading of Sundarī?s loss of voice, this essay offers readings of the depiction of Sundarī?s grief (Beautiful Nanda 6.28-29) and Nanda?s ?disremembering? of her (Beautiful Nanda 7.5-7.9). In conclusion, I suggest that re-reading such passages recommends taking very seriously the possibility that for Aśvaghoṣa there might be a close relationship between the kind of sensitivity his poetry enables and a variety of moral attention.

Aśvaghoṣa and His Canonical Sources (III): The Night of Awakening ( Buddhacarita 14.1–87)

### Abstract

The present paper is the third in a series dedicated to uncovering the canonical sources of Aśvaghoṣa's Buddhacarita and, to the extent possible, the monk-poet's sectarian affiliation. Whereas parts I and II focused on Chapter 16's indebtedness to (Mūla)sarvāstivāda Vinaya and/or Sūtra literature, this third part inquires into the sources of Aśvaghoṣa's account of the Buddha's enlightenment in Chapter 14 (whose first 31 verses have been preserved in their Sanskrit original). Detailed analysis reveals this chapter's intimate relationship with T. 189, a (Mūla)sarvāstivāda (?) biographical sūtra extant in Chinese translation only, but also with textual materials that have come to belong to Mūlasarvāstivāda literature and, as already demonstrated by Kajiyama Yūichi, with the Nagar(opam)asūtra of the Saṃyuktāgama. Among these likely sources, some provide a lively description of the five destinies, others relate to the iconographic prescriptions laid down for drawing the so-called Wheel of saṃsāra/existence, while yet others spell out the doctrine of dependent origination. The detailed comparison of these materials is followed by an admittedly speculative attempt to assess the relationship between these sources.

The Sincerest Form of Flattery: On Imitations of Aśvaghoṣa's Mahākāvyas

### Abstract

Imitations of the works of Aśvaghoṣa, especially the Buddhacarita, are widely attested, both in the form of extra verses interpolated into the texts themselves and of entire texts in Sanskrit and Tocharian (preserved only in fragmentary form) which are restructured versions of Aśvaghoṣa's work. Such imitations and restructurings are here evaluated from the point of view of Sanskrit literary theorists, who describe similar techniques of refashioning pre-existing poems, showing that such works should not be considered as plagiarism but rather as tributes to the original author.

Aśvaghoṣa's Viśeṣaka : The Saundarananda and Its Pāli "Equivalents"

### Abstract

When compared with the Pāli versions of the Nanda tale—the story of the ordainment and liberation of the Buddha's half-brother—some of the peculiar features of Aśvaghoṣa's telling in the Saundarananda come to the fore. These include the enticing love games that Nanda plays with his wife Sundarī before he follows Buddha out of the house, and the powerful, troubling scene in which Buddha forces Nanda to ordain. While the Pāli versions are aware of fantastic elements such as the flight to the Himālayas, and while each adds its own unique emphases that re-shape the events, none raise such deep ambivalence as done by Aśvaghoṣa. The Comparison of the different tellings then raises a more general theoretical point in relation to Buddhist literature—that genre defines the special features of each adaptation of the story, rather than any historical conditions regarding transmission; the versions each conform to the specific intellectual context of the text that appropriates them. This understanding allows an advancement of the idea of genre in Buddhist canonical and semi-canonical texts.

Making It Nice: Kāvya in the Second Century

### Abstract

Around the second century of our era, kāvya steps out from the shadows. What was kāvya at this early moment? What ties together the kāvya produced within the Kuṣāṇa empire in North India, in Sanskrit, with that produced within the Sātavāhana empire of the South, in Prakrit? What ties the Buddhist kāvya of Mātṛceṭa, Aśvaghoṣa, and Kumāralāta to the Jain kāvya of Pālitta and the secular kāvya found in the Seven Centuries? One answer involves the idea of ornamentation (alaṃkāra): the features that, when worked into a text, transform it into an aesthetic object, not simply the "figures" of sound and sense with which this word would later be associated. In the Prakrit texts associated with the Sātavāhana court, ornamentation is essential—the Seven Centuries proclaims that all of its verses have it—but it was just as essential for it to be inconspicuous. The paradox of "artless artifice" was central to the aesthetic of these texts. In the Sanskrit texts of the North, the reverse was the case: massive effort was expended in making the artless appear artful, in casting the teachings and stories of Buddhism as kāvya. I will offer a few speculations about why the North and South took these different "paths," and conclude by connecting them with the later discussion in Sanskrit poetics about the two "paths" of kāvya.

Processions, Seductions, Divine Battles: Aśvaghoṣa at the Foundations of Old Javanese Literature

### Abstract

The influence of Aśvaghoṣa on the later tradition of kāvya was largely passed over in the South Asian tradition, even though the debt to his influence is clear in processional scenes developed by Kālidāsa and the attempted seduction of Arjuna developed by Bhāravi in his Kirātārjunīyam. We know from the testimony of the Chinese pilgrim Yijing that the Buddhacarita was a revered object of study in the Sumatran capital Śrībhoga near the close of the seventh century CE. It thus perhaps comes as no surprise that three tropes or themes developed by Aśvaghoṣa were developed by several important composers of kakawin, the Old Javanese literary genre comparable to the kāvya of South Asia. This paper looks at the development of the themes of processions, divine battles and attempted seductions in a long history beginning with Aśvaghoṣa and closing with the work of the Javanese author Mpu Tantular, who completed the Buddhist kakawin Sutasoma c. 1365–1389 CE. This paper is partly based on a revised perspective on the history of the Shailendra and Sañjaya dynasties of central Java developed by examining the role of the "Shailendra royal preceptors" in bringing Sanskrit learning to Central Java in the period 778–847 CE.

A Bibliography of Aśvaghoṣa

### Abstract

Though quite extensive in its coverage, the present bibliography does not claim to be exhaustive. Among the many works traditionally (but incorrectly) ascribed to Aśvaghoṣa, some, such as the *Mahāyānaśraddhotpādaśāstra (Taishō no. 1666, 1667) or, to a lesser degree, the Kalpanāmaṇḍitikā alias Sūtrālaṅkāra, have lived their own lives in modern scholarship and received virtually as much attention as Aśvaghoṣa himself. An attempt has been made to list all the contributions that have proved decisive in questioning and finally rejecting the poet's authorship of them. In much the same way, most of what has been written about the Chinese and Japanese elaborations of the figure of Aśvaghoṣa (as a patriarch, as a god of sericulture, etc.) has been disregarded. Collecting in a systematic way all Indian editions and translations in modern-day Indian languages (Bengali, Hindi, etc.) has proved practically impossible. Finally, this bibliography does not include all the entries on Aśvaghoṣa in dictionaries, encyclopedias, histories of Indian literature, etc. Only the earliest and the historically or scholarly most significant ones (e.g., those of Winternitz and Keith, and, very recently, Salomon) have found their way into the list. This bibliography would have been even more limited in its coverage had Nobuyoshi Yamabe not generously agreed to include the most important Japanese titles on the subject. In carrying out this task he acknowledges his indebtedness to Kiyoshi Okano's online bibliography (http://gdgdgd.g.dgdg.jp/asvaghosa-index.html). This bibliography is meant as a work in progress. We would like to invite all those who are writing on Aśvaghoṣa to send us their publications or at least detailed references to them so that the bibliography (an online version of which should be available soon) can be regularly updated (vincent.eltschinger@ephe.psl.eu; yamabe@waseda.jp). The sign "†" signals references that were not/could not be accessed directly.

Reading Aśvaghoṣa Across Boundaries: An Introduction

### Abstract

The prominence and the importance of Aśvaghoṣa's works and persona—to the understanding of the history of Sanskrit poetry, to the understanding of Indian Buddhism in a transitional stage and to its introduction to other parts of Asia—is well acknowledged in contemporary scholarship. But with few exceptions the existing scholarship on Aśvaghoṣa has tended to be highly specialized and focused, inviting further reading that builds on this in-depth research to offer an integrated treatment of the variegated aspects and contexts of his works. This special issue of the Journal of Indian Philosophy is intended as a modest step toward a holistic exploration of Aśvaghoṣa works, which reads them across disciplinary as well as regional and temporal boundaries. This introduction is designed to highlight, very schematically, some points of interest and recurring concerns with respect to Aśvaghoṣa works; to point out how the set of articles address these concerns, and to suggest a particular order in which they can be profitably read.

### Computer Assisted Radiology and Surgery

Multi-organ segmentation of the head and neck area: an efficient hierarchical neural networks approach

### Purpose

In radiation therapy, a key step for a successful cancer treatment is image-based treatment planning. One objective of the planning phase is the fast and accurate segmentation of organs at risk and target structures from medical images. However, manual delineation of organs, which is still the gold standard in many clinical environments, is time-consuming and prone to inter-observer variations. Consequently, many automated segmentation methods have been developed.

### Methods

In this work, we train two hierarchical 3D neural networks to segment multiple organs at risk in the head and neck area. First, we train a coarse network on size-reduced medical images to locate the organs of interest. Second, a subsequent fine network on full-resolution images is trained for a final accurate segmentation. The proposed method is purely deep learning based; accordingly, no pre-registration or post-processing is required.

### Results

The approach has been applied on a publicly available computed tomography dataset, created for the MICCAI 2015 Auto-Segmentation challenge. In an extensive evaluation process, the best configurations for the trained networks have been determined. Compared to the existing methods, the presented approach shows state-of-the-art performance for the segmentation of seven different structures in the head and neck area.

### Conclusion

We conclude that 3D neural networks outperform the most existing model- and atlas-based methods for the segmentation of organs at risk in the head and neck area. The ease of use, high accuracy and the test time efficiency of the method make it promising for image-based treatment planning in clinical practice.

A novel image-based retrieval system for characterization of maxillofacial lesions in cone beam CT images

### Purpose

The objective of medical content-based image retrieval (CBIR) is to assist clinicians in decision making by retrieving the most similar cases to a given query image from a large database. Herein, a new method for content-based image retrieval of cone beam CT (CBCT) scans is presented.

### Methods

The introduced framework consists of two main phases: training database construction and querying. The goal of the training phase is database construction, which consists of three main steps. First, automatic segmentation of lesions using 3D symmetry analysis is performed. Embedding the prior shape knowledge of the 3D symmetry characteristics of the healthy human head structure increases the accuracy of automatic segmentation. Then, spatial pyramid matching is used for feature extraction, and the relative importance of each feature is learned using classifiers.

### Results

The method was applied to a dataset of 1145 volumetric CBCT images with four classes of maxillofacial lesions. A symmetry-based analysis model for automatic lesion segmentation was evaluated using similarity measures. Mean Dice coefficients of 0.89, 0.85, 0.92, and 0.87 were achieved for maxillary sinus perforation, radiolucent lesion, unerupted tooth, and root fracture classes, respectively. Moreover, the execution time of automatic segmentation was reduced to 3 min per case. The performance of the proposed search engine was evaluated using mean average precision and normalized discounted cumulative gain. A mean average retrieval accuracy and normalized discounted cumulative gain of 0.90 and 0.92, respectively, were achieved.

### Conclusion

Quantitative results show that the proposed approach is more effective than previous methods in the literature, and it can facilitate the introduction of CBIR in clinical CBCT applications.

EyeSAM: graph-based localization and mapping of retinal vasculature during intraocular microsurgery

### Purpose

Robot-assisted intraocular microsurgery can improve performance by aiding the surgeon in operating on delicate micron-scale anatomical structures of the eye. In order to account for the eyeball motion that is typical in intraocular surgery, there is a need for fast and accurate algorithms that map the retinal vasculature and localize the retina with respect to the microscope.

### Methods

This work extends our previous work by a graph-based SLAM formulation using a sparse incremental smoothing and mapping (iSAM) algorithm.

### Results

The resulting technique, "EyeSAM," performs SLAM for intraoperative vitreoretinal surgical use while avoiding spurious duplication of structures as with the previous simpler technique. The technique also yields reduction in average pixel error in the camera motion estimation.

### Conclusions

This work provides techniques to improve intraoperative tracking of retinal vasculature by handling loop closures and achieving increased robustness to quick shaky motions and drift due to uncertainties in the motion estimation.

Interactive patient-customized curvilinear reformatting for improving neurosurgical planning

### Purpose

Visualizing a brain in its native space plays an essential role during neurosurgical planning because it allows the superficial cerebral veins and surrounding regions to be preserved. This paper describes the use of a visualization tool in which single gadolinium contrast-enhanced T1-weighted magnetic resonance imaging was applied in nondefective and nonresective skulls to promote visualization of important structures.

### Methods

A curvilinear reformatting tool was applied on the supratentorial compartment to peel the tissues to the depth of the dura mater and thereby revealing cortical and vascular spatial relationships. The major advantage of our proposed tool is that it does not require coregistration of anatomical and vascular volumes.

### Results

The reliability of this technique was supported by comparisons between preoperative images and digital photographs of the brain cortical surface obtained after the dura mater was removed in 20 patients who underwent surgery in the Clinics Hospital of the University of Campinas from January 2017 to April 2018.

### Conclusion

Single fat-suppressed GAD contrast-enhanced T1-weighted magnetic resonance scans provide accurate preoperative 3D views of cortical and vascular relationships similar to neurosurgeons' intraoperative views. In developing countries with limited access to state-of-the-art health technologies, this imaging approach may improve the safety of complex neurosurgeries.

A direct volume rendering visualization approach for serial PET–CT scans that preserves anatomical consistency

### Purpose

Our aim was to develop an interactive 3D direct volume rendering (DVR) visualization solution to interpret and analyze complex, serial multi-modality imaging datasets from positron emission tomography–computed tomography (PET–CT).

### Methods

Our approach uses: (i) a serial transfer function (TF) optimization to automatically depict particular regions of interest (ROIs) over serial datasets with consistent anatomical structures; (ii) integration of a serial segmentation algorithm to interactively identify and track ROIs on PET; and (iii) parallel graphics processing unit (GPU) implementation for interactive visualization.

### Results

Our DVR visualization more easily identifies changes in ROIs in serial scans in an automated fashion and parallel GPU computation which enables interactive visualization.

### Conclusions

Our approach provides a rapid 3D visualization of relevant ROIs over multiple scans, and we suggest that it can be used as an adjunct to conventional 2D viewing software from scanner vendors.

Missed paranasal sinus compartments in sinus surgery with and without image-guidance systems: a pilot feasibility study

### Purpose

Image-guidance systems (IGS) have gained widespread use in endoscopic sinus surgery (ESS) and have been thoroughly analysed. In this study, we looked for a new parameter to determine if patients could directly benefit from the use of IGS during primary ESS. We questioned if IGS could improve the quality of ESS in chronic rhinosinusitis (CRS) patients via allowing a more comprehensive treatment of all involved sinus compartments.

### Methods

In a pilot feasibility study, we evaluated uncomplicated CRS patients following primary ESS with and without IGS between January 2011 and June 2012 using preoperative and postoperative CT scans. The preoperative CT scans identified the sinus compartments requiring surgery. The postoperative CT scans were used to evaluate the treatment effect in these compartments. From these data, we calculated a missing ratio (missed compartments/compartments requiring surgery) for each patient.

### Results

Of the 169 ESS patients who were treated, ten patients were retrospectively identified as complying with the inclusion and exclusion criteria following ESS with IGS. Ten patients treated without IGS were then randomly chosen. The median missing ratio for non-IGS patients was 36%, and for IGS patients, the median missing ratio was 0% (p = 0.046). However, the missing ratio was depended on the number of compartments requiring surgery. Stratification of the number of compartments requiring surgery resulted in an exact p value of 0.13.

### Conclusions

IGS could help the surgeon to more completely address diseased sinus compartments. For better scientific merit, a comparative study of ESS with and without IGS seems feasible, using the proposed failing score missed compartments/compartments requiring surgery as the primary outcome parameter.

Random forest classifiers aid in the detection of incidental osteoblastic osseous metastases in DEXA studies

### Purpose

Dual-energy X-ray absorptiometry (DEXA) studies are used for screening patients for low bone mineral density (BMD). Patients with breast and prostate cancer are often treated with hormone-altering drugs that result in low BMD. These patients may have incidental osteoblastic metastases of the spine that may be detected on screening DEXA studies. The aim of this pilot study is to assess whether random forest classifiers or support vector machines can identify patients with incidental osteoblastic metastases of the spine from screening DEXA studies and to evaluate which technique is better.

### Methods

We retrospectively reviewed the DEXA studies from 200 patients (155 normal control patients and 45 patients with osteoblastic metastases of one or more lumbar vertebral bodies from L1 to L4). The dataset was split into training (80%) and validation (20%) datasets. The optimal random forest (RF) and support vector machine (SVM) classifiers were obtained. Receiver-operator-characteristic curves were compared with DeLong's test.

### Results

The sensitivity, specificity, accuracy and area under the curve (AUC) of the optimal RF classifier were 77.8%, 100.0%, 98.0% and 0.889, respectively, in the validation dataset. The sensitivity, specificity, accuracy and AUC of the optimal SVM classifier were 33.3%, 96.8%, 82.5% and 0.651 in the validation dataset. The RF classifier was significantly better than the SVM classifier (P = 0.008). Only 7 of the 45 patients with osteoblastic metastases (15.6%) were prospectively identified by the radiologist interpreting the study.

### Conclusions

RF classifiers can be used as a useful adjunct to identify incidental lumbar spine osteoblastic metastases in screening DEXA studies.

A novel multiple communication paths for surgical telepresence videos delivery of the maxilla area in oral and maxillofacial surgery

### Purpose

A surgical telepresence between two surgical sites where a local surgeon in the surgery site, who is less experienced, needs help from the expert surgeon located at a remote site. Furthermore, the primary aim of this paper is to improve the quality of surgical video sent and received to-and-from both surgical sites, which has been a major quality issue so far.

### Method

This work considers flow rate allocation and resource availability to determine the network path quality. Furthermore, a segmented backup path is used to provide a timely recovery in case of failure in the link. A neighbour detection technique in segmented backup is used to reduce the detection latency of the network in case of link failure.

### Results

The results depict that the proposed system improves the quality of the surgical video by an average of 5.5 db over the current system. Furthermore, the neighbour detection technique detects the network failure 40–45% faster than the currently used end-to-end detection system. The experimental results have done on the maxilla areas in oral and maxillofacial surgery.

### Conclusion

The proposed system concentrates on reducing the network failure detection latency and improves the received and sent video quality by using an enhanced path quality technique. Thus, this study enhances the video quality and provides a backup option in case of failure, which offers timely recovery for communication between two surgeons.

A practical marker-less image registration method for augmented reality oral and maxillofacial surgery

### Background

Image registration lies in the core of augmented reality (AR), which aligns the virtual scene with the reality. In AR surgical navigation, the performance of image registration is vital to the surgical outcome.

### Methods

This paper presents a practical marker-less image registration method for AR-guided oral and maxillofacial surgery where a virtual scene is generated and mixed with reality to guide surgical operation or provide surgical outcome visualization in the manner of video see-through overlay. An intraoral 3D scanner is employed to acquire the patient's teeth shape model intraoperatively. The shape model is then registered with a custom-made stereo camera system using a novel 3D stereo matching algorithm and with the patient's CT-derived 3D model using an iterative closest point scheme, respectively. By leveraging the intraoral 3D scanner, the CT space and the stereo camera space are associated so that surrounding anatomical models and virtual implants could be overlaid on the camera's view to achieve AR surgical navigation.

### Results

Jaw phantom experiments were performed to evaluate the target registration error of the overlay, which yielded an average error of less than 0.50 mm with the time cost less than 0.5 s. Volunteer trial was also conducted to show the clinical feasibility.

### Conclusions

The proposed registration method does not rely on any external fiducial markers attached to the patient. It performs automatically so as to maintain a correct AR scene, overcoming the misalignment difficulty caused by patient's movement. Therefore, it is noninvasive and practical in oral and maxillofacial surgery.

Subject-specific modelling of pneumoperitoneum: model implementation, validation and human feasibility assessment

### Purpose

The aim of this study is to propose a model that simulates patient-specific anatomical changes resulting from pneumoperitoneum, using preoperative data as input. The framework can assist the surgeon through a real-time visualisation and interaction with the model. Such could further facilitate surgical planning preoperatively, by defining a surgical strategy, and intraoperatively to estimate port positions.

### Methods

The biomechanical model that simulates pneumoperitoneum was implemented within the GPU-accelerated NVIDIA FleX position-based dynamics framework. Datasets of multiple porcine subjects before and after abdominal insufflation were used to generate, calibrate and validate the model. The feasibility of modelling pneumoperitoneum in human subjects was assessed by comparing distances between specific landmarks from a patient abdominal wall, to the same landmark measurements on the simulated model.

### Results

The calibration of simulation parameters resulted in a successful estimation of an optimal set parameters. A correspondence between the simulation pressure parameter and the experimental insufflation pressure was determined. The simulation of pneumoperitoneum in a porcine subject resulted in a mean Hausdorff distance error of 5–6 mm. Feasibility of modelling pneumoperitoneum in humans was successfully demonstrated.

### Conclusion

Simulation of pneumoperitoneum provides an accurate subject-specific 3D model of the inflated abdomen, which is a more realistic representation of the intraoperative scenario when compared to preoperative imaging alone. The simulation results in a stable and interactive framework that performs in real time, and supports patient-specific data, which can assist in surgical planning.

### Molecular and Cellular Neuroscience

Klotho deficiency affects the spine morphology and network synchronization of neurons

Publication date: Available online 13 April 2019

Source: Molecular and Cellular Neuroscience

Author(s): Hai T. Vo, Mary L. Phillips, Jeremy H. Herskowitz, Gwendalyn D. King

##### Abstract

Klotho-deficient mice rapidly develop cognitive impairment and show some evidence of the onset of neurodegeneration. However, it is impossible to investigate the long-term consequences on the brain because of the dramatic shortening of lifespan caused by systemic klotho deficiency. As klotho expression is downregulated with advancing organismal age, understanding the mechanisms of klotho action is important for developing novel strategies to support healthy brain aging. Previously, we reported that klotho-deficient mice show enhanced long-term potentiation prior to the onset of cognitive impairment. To inform this unusual phenotype, herein, we examined neuronal structure and in vitro synaptic function. Our results indicate that klotho deficiency causes the population of dendritic spines to shift towards increased head diameter and decreased length consistent with mature, mushroom type spines. Multi-electrode array recordings from klotho-deficient neurons show increased synchronous firing and activity changes reflective of increased neuronal network activity. Supplementation of the neuronal growth media with recombinant shed klotho corrected some but not all of the activity changes caused by KL deficiency. Last, in vivo we found that klotho-deficient mice have a decreased latency to induced seizure activity. Together these data show that klotho-deficient memory impairments are underpinned by structural and functional changes that may preclude ongoing normal cognition.

An FTLD-associated SQSTM1 variant impacts Nrf2 and NF-κB signalling and is associated with reduced phosphorylation of p62

Publication date: Available online 4 April 2019

Source: Molecular and Cellular Neuroscience

Author(s): A. Foster, D. Scott, R. Layfield, S.L. Rea

##### Abstract

Elevated oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). In response to oxidative stress, the Nrf2 transcription factor activates protective antioxidant genes. A critical regulator of Nrf2 is the inhibitory protein Keap1, which mediates Nrf2 degradation. In response to cellular stress an interaction between Keap1 and SQSTM1/p62 (p62), a signalling adaptor protein, allows for increased Nrf2 signalling as it escapes degradation. Mutations in SQSTM1 (encoding p62) are linked with ALS-FTLD. Previously, two ALS-FTLD-associated p62 mutant proteins within the Keap1 interacting region (KIR) of p62 were found to be associated with decreased Keap1-p62 binding and Nrf2 activation. Here we report that a non-KIR domain FTLD-associated variant of p62 (p.R110C), affecting a residue close to the N-terminal PB1 oligomerisation domain, also reduces Keap1-p62 binding in cellulo and thereby reduces Nrf2 activity in reporter assays. Further, we observed that expression of p.R110C increased NF-κB activation compared with wild type p62. Altered signalling appeared to be linked with reduced phosphorylation of p62 at Serine residues −349 and −403. Our results confirm that ALS-FTLD mutations affecting multiple domains of p62 result in a reduced stress response, suggesting that altered stress signalling may directly contribute to the pathology of some ALS-FTLD cases.

Small molecules as therapeutic drugs for Alzheimer's disease

Publication date: April 2019

Source: Molecular and Cellular Neuroscience, Volume 96

Author(s): Darryll M.A. Oliver, P. Hemachandra Reddy

##### Abstract

Mitochondrial dysfunction is a central protagonist of Alzheimer's disease (AD) pathogenesis. Mitochondrial dysfunction stems from various factors including mitochondrial DNA damage and oxidative stress from reactive oxygen species, membrane and ionic gradient destabilization, and interaction with toxic proteins such as amyloid beta (Aβ). Therapeutic drugs such as cholinesterase and glutamate inhibitors have proven to improve synaptic neurotransmitters, but do not address mitochondrial dysfunction. Researchers have demonstrated that oxidative damage may be reduced by increasing endogenous antioxidants, and/or increasing exogenous antioxidants such as vitamin C & E, beta-carotene and glutathione. Nonetheless, as AD pathology intensifies, endogenous antioxidants are overwhelmed, and exogenous antioxidants are unable to reach neuronal mitochondria as they are blocked by the blood brain barrier. Current therapeutic methods however include novel usage of lipophilic phosphonium cation bound to antioxidants, to effect neuronal mitochondria targeted activity. Mitochondria targeted MitoQ, MitoVitE, MitoTempo, MitoPBN and MCAT concentrate within mitochondria where they scavenge free-radicals, and augment mitochondrial dysfunction. Additional molecules include Szeto-Schiller (SS) peptides which target stability of the inner mitochondrial membrane, and DDQ molecule capable of improving bioenergetics and reduce mitochondrial fragmentation. This article discusses advantages and disadvantages of small molecules, their ability to mitigate Aβ induced damage, and ability to ameliorate synaptic dysfunction and cognitive loss.

Growth and excitability at synapsin II deficient hippocampal neurons

Publication date: April 2019

Source: Molecular and Cellular Neuroscience, Volume 96

Author(s): Heidi Matos, Raymond Quiles, Rodrigo Andrade, Maria Bykhovskaia

##### Abstract

Synapsins are neuronal phosphoproteins that fine-tune synaptic transmission and suppress seizure activity. Synapsin II (SynII) deletion produces epileptic seizures and overexcitability in neuronal networks. Early studies in primary neuronal cultures have shown that SynII deletion results in a delay in synapse formation. More recent studies at hippocampal slices have revealed increased spontaneous activity in SynII knockout (SynII(−)) mice. To reconcile these observations, we systematically re-examined synaptic transmission, synapse formation, and neurite growth in primary hippocampal neuronal cultures. We find that spontaneous glutamatergic synaptic activity was suppressed in SynII(−) neurons during the initial developmental epoch (7 days in vitro, DIV) but was enhanced at later times (12 and18 DIV). The density of synapses, transmission between connected pairs of neurons, and the number of docked synaptic vesicles were not affected by SynII deletion. However, we found that neurite outgrowth in SynII(−) neurons was suppressed during the initial developmental epoch (7 DIV) but enhanced at subsequent developmental stages (12 and18 DIV). This finding can account for the observed effect of SynII deletion on synaptic activity. To test whether the observed phenotype resulted directly from the deletion of SynII we expressed SynII in SynII(−) cultures using an adeno-associated virus (AAV). Expression of SynII at 2 DIV rescued the SynII deletion-dependent alterations in both synaptic activity and neuronal growth. To test whether the increased neurite outgrowth in SynII(−) observed at DIV 12 and18 represents an overcompensation for the initial developmental delay or results directly from SynII deletion we performed "late expression" experiments, transfecting SynII(−) cultures with AAV at 7 DIV. The late SynII expression suppressed neurite outgrowth at 12 and 18 DIV to the levels observed in control neurons, suggesting that these phenotypes directly depend on SynII. These results reveal a novel developmentally regulated role for SynII function in the control of neurite growth.

Taxifolin protects neurons against ischemic injury in vitro via the activation of antioxidant systems and signal transduction pathways of GABAergic neurons

Publication date: April 2019

Source: Molecular and Cellular Neuroscience, Volume 96

Author(s): M.V. Turovskaya, S.G. Gaidin, V.N. Mal'tseva, V.P. Zinchenko, E.A. Turovsky

##### Abstract

Cerebral blood flow disturbances lead to the massive death of brain cells. The death of >80% of cells is observed in hippocampal cell cultures after 40 min of oxygen and glucose deprivation (ischemia-like conditions, OGD). However, there are some populations of GABAergic neurons which are characterized by increased vulnerability to oxygen-glucose deprivation conditions. Using fluorescent microscopy, immunocytochemical assay, vitality tests and PCR-analysis, we have shown that population of GABAergic neurons are characterized by a different (faster) Ca2+ dynamics in response to OGD and increased basal ROS production under OGD conditions. A plant flavonoid taxifolin inhibited an excessive ROS production and an irreversible cytosolic Ca2+ concentration increase in GABAergic neurons, preventing the death of these neurons and further excitation of a neuronal network; neuroprotective effect of taxifolin increased after incubation of 24 h and correlated with increased expression of antiapoptocic and antioxidant genes Stat3 Nrf-2 Bcl-2, Bcl-xL, Ikk2, and genes coding for AMPA and kainate receptor subunits; in addition, taxifolin decreased expression of prooxidant enzyme NOS and proinflammatory cytokine IL-1β.

Neurotoxic effects of MPTP on mouse cerebral cortex: Modulation of neuroinflammation as a neuroprotective strategy

Publication date: April 2019

Source: Molecular and Cellular Neuroscience, Volume 96

Author(s): Mariana Oliveira Mendes, Alexandra Isabel Rosa, Andreia Neves Carvalho, Maria João Nunes, Pedro Dionísio, Elsa Rodrigues, Daniela Costa, Sara Duarte-Silva, Patrícia Maciel, Cecília Maria Pereira Rodrigues, Maria João Gama, Margarida Castro-Caldas

##### Abstract

Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled.

Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that has been shown to have antioxidant properties and to exhibit a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. Moreover, TUDCA anti-inflammatory properties have been reported in glial cells, making it a prominent therapeutic agent in PD.

Here, we used C57BL/6 mice injected with MPTP in a sub-acute paradigm aiming to investigate if the neurotoxic effects of MPTP could be extended to the cerebral cortex. In parallel, we evaluated the anti-oxidant, neuroprotective and anti-inflammatory effects of TUDCA. The anti-inflammatory mechanisms elicited by TUDCA were further dissected in microglia cells.

Our results show that MPTP leads to a decrease of ATP and activated AMP-activated protein kinase levels in mice cortex, and to a transient increase in the expression of antioxidant downstream targets of nuclear factor erythroid 2 related factor 2 (Nrf-2), and parkin. Notably, MPTP increases pro-inflammatory markers, while down-regulating the expression of the anti-inflammatory protein Annexin-A1 (ANXA1). Importantly, we show that TUDCA treatment prevents the deleterious effects of MPTP, sustains increased levels of antioxidant enzymes and parkin, and most of all negatively modulates neuroinflammation and up-regulates ANXA1 expression. Additionally, results from cellular models using microglia corroborate TUDCA modulation of ANXA1 synthesis, linking inhibition of neuroinflammation and neuroprotection by TUDCA.

Modulation of Cav2.3 channels by unconjugated bilirubin (UCB) – Candidate mechanism for UCB-induced neuromodulation and neurotoxicity

Publication date: April 2019

Source: Molecular and Cellular Neuroscience, Volume 96

Author(s): Walid Albanna, Jan Niklas Lüke, Gerrit Alexander Schubert, Maxine Dibué-Adjei, Konstantin Kotliar, Jürgen Hescheler, Hans Clusmann, Hans-Jakob Steiger, Daniel Hänggi, Marcel A. Kamp, Toni Schneider, Felix Neumaier

##### Abstract

Elevated levels of unbound unconjugated bilirubin (UCB) can lead to bilirubin encephalopathy and kernicterus. In spite of a large number of studies demonstrating UCB-induced changes in central neurotransmission, it is still unclear whether these effects involve alterations in the function of specific ion channels. To assess how different UCB concentrations and UCB:albumin (U/A) molar ratios affect neuronal R-type voltage-gated Ca2+channels, we evaluated their effects on whole-cell currents through recombinant Cav2.3 + β3 channel complexes and ex-vivo electroretinograms (ERGs) from wildtype and Cav2.3-deficient mice. Our findings show that modestly elevated levels of unbound UCB (U/A = 0.5) produce subtle but significant changes in the voltage-dependence of activation and prepulse inactivation, resulting in a stimulation of currents activated by weak depolarization and inhibition at potentials on the plateau of the activation curve. Saturation of the albumin binding capacity (U/A = 1) produced additional suppression that became significant when albumin was omitted completely and might involve a complete loss of channel function.

Acutely administered UCB (U/A = 0.5) has recently been shown to affect transsynaptic signaling in the isolated vertebrate retina. The present report reveals that sustained exposure of the murine retina to UCB significantly suppresses also late responses of the inner retina (b-wave) from wildtype compared to Cav2.3-deficient mice. In addition, recovery during washout was significantly more complete and faster in retinae lacking Cav2.3 channels.

Together, these findings show that UCB affects cloned and native Cav2.3 channels at clinically relevant U/A molar ratios and indicate that supersaturation of albumin is not required for modulation but associated with a loss of channel functional that could contribute to chronic neuronal dysfunction.

Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity

Publication date: March 2019

Source: Molecular and Cellular Neuroscience, Volume 95

Author(s): Shehla U. Hridi, Aimée J.P.M. Franssen, Hui-Rong Jiang, Trevor J. Bushell

##### Abstract

Interleukin 16 (IL-16) is a cytokine that is primarily associated with CD4+ T cell function, but also exists as a multi-domain PDZ protein expressed within cerebellar and hippocampal neurons. We have previously shown that lymphocyte-derived IL-16 is neuroprotective against excitotoxicity, but evidence of how it affects neuronal function is limited. Here, we have investigated whether IL-16 modulates neuronal excitability and synaptic activity in mouse primary hippocampal cultures. Application of recombinant IL-16 impairs both glutamate-induced increases in intracellular Ca2+ and sEPSC frequency and amplitude in a CD4- and CD9-independent manner. We examined the mechanisms underlying these effects, with rIL-16 reducing GluA1 S831 phosphorylation and inhibiting Na+ channel function. Taken together, these data suggest that IL-16 reduces neuronal excitability and synaptic activity via multiple mechanisms and adds further evidence that alternative receptors may exist for IL-16.

Sympathomimetics regulate neuromuscular junction transmission through TRPV1, P/Q- and N-type Ca2+ channels

Publication date: March 2019

Source: Molecular and Cellular Neuroscience, Volume 95

Author(s): Anna Zaia Carolina Rodrigues, Zhong-Min Wang, María Laura Messi, Osvaldo Delbono

##### Abstract

Increasing evidence indicates that, first, the sympathetic nervous system interacts extensively with both vasculature and skeletal muscle fibers near neuromuscular junctions (NMJs) and, second, its neurotransmitter, noradrenaline, influences myofiber molecular composition and function and motor innervation. Since sympathomimetic agents have been reported to improve NMJ transmission, we examined whether two in clinical use, salbutamol and clenbuterol, affect the motor axon terminal via extracellular Ca2+ and molecular targets, such as TRPV1 and P/Q- and N-type voltage-activated Ca2+ channels. Electrophysiological recordings in ex-vivo preparations of peroneal nerves and lumbricalis muscles from young adult mice focused on spontaneous miniature end-plate potentials and singly and repetitively evoked end-plate potentials. Adding one dose of salbutamol or clenbuterol to the nerve/muscle preparation or repeatedly administering salbutamol to a mouse for 4 weeks increased spontaneous and evoked synaptic vesicle release but induced a steep decline in EPP amplitude in response to repetitive nerve stimulation. These effects were mediated primarily by ω-agatoxin IVA-sensitive P/Q-type and secondarily by ω-conotoxin GVIA-sensitive N-type Ca2+ channels. Presynaptic arvanil-sensitive TRPV1 channels seem to regulate Ca2+ at the motor neuron terminal at rest, while putative presynaptic β-adrenergic receptors may mediate sympathomimetic and catecholamine effects on presynaptic Ca2+channels during NMJ activation.

Norepinephrine control of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter expression in the female rat: Role of monocarboxylate transporter function

Publication date: March 2019

Source: Molecular and Cellular Neuroscience, Volume 95

Author(s): A.S.M. Hasan Mahmood, Santosh K. Mandal, Khaggeswar Bheemanapally, Mostafa M.H. Ibrahim, K.P. Briski

##### Abstract

The ventromedial hypothalamic nucleus (VMN) is a critical component of the neural circuitry that regulates glucostasis. Astrocyte glycogen is a vital reserve of glucose and its oxidizable metabolite L-lactate. In hypoglycemic female rats, estradiol-dependent augmentation of VMN glycogen phosphorylase (GP) protein requires hindbrain catecholamine input. Research here investigated the premise that norepinephrine (NE) regulation of VMN astrocyte metabolism shapes local glucoregulatory neurotransmitter signaling in this sex. Estradiol-implanted ovariectomized rats were pretreated by intra-VMN administration of the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxy-cinnamic acid (4CIN) or vehicle before NE delivery to that site. NE caused 4CIN-reversible reduction or augmentation of VMN glycogen synthase and phosphorylase expression. 4CIN prevented NE stimulation of gluco-inhibitory (glutamate decarboxylase65/67) and suppression of gluco-stimulatory (neuronal nitric oxide synthase) neuron marker proteins. These outcomes imply that effects of noradrenergic stimulation of VMN astrocyte glycogen depletion on glucoregulatory transmitter signaling may be mediated, in part, by glycogen-derived substrate fuel provision. NE control of astrocyte glycogen metabolism may involve down-regulated adrenoreceptor (AR), e.g. alpha1 and alpha2, alongside amplified beta1 AR and estrogen receptor-beta signaling. Noradrenergic hypoglycemia was refractory to 4CIN, implying that additional NE-sensitive VMN glucoregulatory neurochemicals may be insensitive to monocarboxylate uptake. Augmentation of circulating free fatty acids by combinatory NE and 4CIN, but not NE alone implies that acute hypoglycemia induced here is an insufficient stimulus for mobilization of these fuels, but is adequate when paired with diminished brain monocarboxylate fuel availability.