Process Parameters Optimization, Characterization, and Application of KOH-Activated Norway Spruce Bark Graphitic Biochars for Efficient Azo Dye Adsorption.

In this work, Norway spruce bark was used as a precursor to prepare activated biochars (BCs) via chemical activation with potassium hydroxide (KOH) as a chemical activator. A Box-Behnken design (BBD) was conducted to evaluate and identify the optimal conditions to reach high specific surface area and high mass yield of BC samples. The studied BC preparation parameters and their levels were as follows: pyrolysis temperature (700, 800, and 900 °C), holding time (1, 2, and 3 h), and ratio of the biomass: chemical activator of 1: 1, 1.5, and 2. The planned BBD yielded BC with extremely high SSA values, up to 2209 m2·g-1. In addition, the BCs were physiochemically characterized, and the results indicated that the BCs exhibited disordered carbon structures and presented a high quantity of O-bearing functional groups on their surfaces, which might improve their adsorption performance towards organic pollutant removal. The BC with the highest SSA value was then employed as an adsorbent to remove Evans blue dye (EB) and colorful effluents. The kinetic study followed a general-order (GO) model, as the most suitable model to describe the experimental data, while the Redlich-Peterson model fitted the equilibrium data better. The EB adsorption capacity was 396.1 mg·g-1. The employment of the BC in the treatment of synthetic effluents, with several dyes and other organic and inorganic compounds, returned a high percentage of removal degree up to 87.7%. Desorption and cyclability tests showed that the biochar can be efficiently regenerated, maintaining an adsorption capacity of 75% after 4 adsorption-desorption cycles. The results of this work pointed out that Norway spruce bark indeed is a promising precursor for producing biochars with very promising properties.

Plasma volume expansion across healthy pregnancy: a systematic review and meta-analysis of longitudinal studies.

BACKGROUND: Plasma volume expansion is an important physiologic change across gestation. High or low expansion has been related to adverse pregnancy outcomes, yet there is a limited understanding of normal/healthy plasma volume expansion. We aimed to evaluate the pattern of plasma volume expansion across healthy pregnancies from longitudinal studies. METHODS: We conducted a systematic review and meta-analysis to identify original studies that measured plasma volume in singleton pregnancies of healthy women. Specifically, we included studies that measured plasma volume at least two times across gestation and one time before or after pregnancy in the same women. PubMed, Web of Science, Cochrane, CINAHL, and clinicaltrials.gov databases were searched from the beginning of each database to February 2019. We combined data across studies using a random effects model. RESULTS: Ten observational studies with a total of 347 pregnancies were eligible. Plasma volume increased by 6% (95% CI 3-9) in the first trimester compared to the nonpregnant state. In the second trimester, plasma volume was increased by 18% (95% CI 12-24) in gestational weeks 14-20 and 29% (95% CI 21-36) in weeks 21-27 above the nonpregnant state. In the third trimester, plasma volume was increased by 42% (95% CI 38-46) in weeks 28-34 and 48% (95% CI 44-51) in weeks 35-38. The highest rate of increase occurred in the first half of the second trimester. Included studies were rated from moderate to high quality; 7 out of 10 studies were conducted over 30 years ago. CONCLUSIONS: In healthy pregnancies, plasma volume begins to expand in the first trimester, has the steepest rate of increase in the second trimester, and peaks late in the third trimester. The patterns observed from these studies may not reflect the current population, partly due to the changes in BMI over the last several decades. Additional longitudinal studies are needed to better characterize the range of normal plasma volume expansion across maternal characteristics.

Low-Dose Evans Blue Dye for Near-Infrared Fluorescence Imaging in Photothrombotic Stroke Model.

Background: Evans blue dye (EBD) is the most common indicator to analyze the extent of blood-brain barrier (BBB) breakdown in several neurological disease models. However, the high-dose of EBD (51.9 mg/kg) is usually required for visualization of blue color by the human eye that brings potential safety issues. Methods: To solve this problem, low-dose of EBD was applied for the near-infrared (NIR) fluorescence-assisted quantitation of BBB breakdown in photothrombotic stoke model. Animals were allocated to seven dose groups ranging from 1.35 nmol (5.19 µg/kg) to 13.5 µmol (51.9 mg/kg) EBD. Results: EBD was undetectable in the non-ischemic brain tissue, and the fluorescence signals in the infarcted hemisphere seemed proportional to the injected dose in the dose range. Although the maximum fluorescence signals in brain tissue were obtained with the injections of 1.35 nmol ~ 13.5 µmol EBD, the background signals in the neighboring brain tissues were significantly increased as well. Since the high concentration of EBD is necessary for color-based identification of the infarcted lesion in brain tissues, even 10-fold diluted could not be distinguished visually by naked eye. Conclusions: NIR fluorescence-assisted method could potentially provide new opportunities to study BBB leakage just using small amount of EBD in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB.

Microsurgery guided by sequential preoperative lymphography using 68Ga-NEB PET and MRI in patients with lower-limb lymphedema.

OBJECTIVE: The popularity of contemporary microsurgical techniques in treatment of lower-limb lymphedema calls for better visualization of the lymphatic system, both preoperatively and intra-operatively. The aim of this prospective study was to investigate the feasibility of a novel combination of 68Ga-NEB positron emission tomography (PET) with magnetic resonance lymphography (MRL) in evaluating lymphedema and guiding surgical intervention. METHODS: A total of 11 patients (F 9, M 2, age range 29-69 y) with lower-limb lymphedema classified into stage I to III were recruited. PET acquisition was performed at 30, 60 and 90 min after subcutaneous injection of the albumin-binding radiotracer 68Ga-NEB into the bilateral first web spaces of the feet. All the patients were also subjected to 99mTc-sulfur colloid (SC) lymphoscintigraphy for comparison. Gd-DTPA-enhanced magnetic resonance imaging (MRI) was performed using sequences specialized for lymphatic vessel scans. All the patients underwent surgical interventions within a week. The surgical approach includes the use of a linear marker for edema localization and indocyanine green (ICG) lymphography with a near-infrared surgical navigation system intra-operatively. RESULTS: Lymph transport in lymphatic channels was clearly observed by visualization of 68Ga-NEB activity in the lymphatic vessels and within lymph nodes for all 11 patients as well as the visualization of the edema section plane with dermal backflow (DB), abnormally increased and disconnected uptake along the lymphatic channels. Preoperative 68Ga-NEB PET combined with MRL provides advantageous three-dimensional images, higher temporal resolution, significantly shorter time lapse before image acquisition after tracer injection and more accurate pathological lymphatic vessel distribution than 99mTc-SC lymphoscintigraphy combined with MRI. CONCLUSION: This study documented an effective imaging pattern to combine 68Ga-NEB PET and MRL in patients with lower-limb lymphedema. This strategy demonstrated significant advantage over 99mTc-SC lymphoscintigraphy/MRL in the evaluation of lymphedema severity, staging and pathological location of lymph vessels to make an individualized treatment plan. Dual 68Ga-NEB PET/MRL is thus recommended before the operation for staging and therapy planning.

A New Modified Evans Blue Dye Test as Screening Test for Aspiration in Tracheostomized Patients.

OBJECTIVE: The authors assessed the diagnostic accuracy of a new modified Evans blue dye test (MEBDT) as a screening test for aspiration in tracheostomized patients. DESIGN: Monocentric retrospective study performed between October 2013 and December 2015. SETTING: Anesthesia and Intensive Care Unit, Second University of Naples. PARTICIPANTS: Among 62 eligible patients, 5 were excluded. The authors' study population included 57 patients. INTERVENTIONS: Patients underwent both fiberoptic endoscopic examination of the swallow (FEES) and MEBDT to evaluate swallow. The MEBDT results were compared with those of FEES and the diagnostic accuracy of MEBDT was calculated using the FEES as the gold standard. MEASUREMENTS AND MAIN RESULTS: The authors found that both FEES and MEBDT were positive for aspiration in 40 patients (true-positive MEBDT); FEES and MEBDT were negative in 10 (true-negative MEBDT). On the other hand, FEES was positive with an MEBDT negative in 7 patients (false-negative MEBDT), and there were no FEES negative and MEBDT positive (false-positive MEBDT). MEBDT had a sensitivity, specificity, positive, and negative predicted value of 85%, 100%, 100%, and 58.82%, respectively. CONCLUSIONS: MEBDT could be a supplementary diagnostic test for aspiration. Patients with positive MEBDT should not undergo oral feeding, while patients with negative MEBDT should undergo FEES before starting oral feeding.

Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, p<0.05) in rat neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. In further studies (studies 1-4), in vivo AMI was induced by 30min coronary occlusion and 120min reperfusion in male Wistar rats. Test compounds and positive controls for model validation (B-type natriuretic peptide, BNP or cyclosporine A, CsA) were administered iv. before the onset of reperfusion. Infarct size (IS) was measured by standard TTC staining. In study 1, 5000U/kg EPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, p<0.05). In study 2, darbepoetin showed a U-shaped dose-response curve with maximal infarct size-reducing effect at 5µg/kg compared to the vehicle (44.4±5.7% vs. 65.9±2.7%, p<0.01). In study 3, AF41676 showed a U-shaped dose-response curve, where 3mg/kg was the most effective dose compared to the vehicle (24.1±3.9% vs. 44.3±2.5%, p<0.001). The positive control BNP significantly decreased infarct size in studies 1-3 by approximately 35%. In study 4, AF43136 at 10mg/kg decreased infarct size, similarly to the positive control CsA compared to the appropriate vehicle (39.4±5.9% vs. 58.1±5.4% and 45.9±2.4% vs. 63.8±4.1%, p<0.05, respectively). This is the first demonstration that selective, non-erythropoietic EPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce infarct size in a rat model of AMI. Therefore, non-erythropoietic EPO receptor peptide ligands may be promising cardioprotective agents.

Simvastatin attenuates sepsis-induced blood-brain barrier integrity loss.

BACKGROUND: Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. METHODS: A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. RESULTS: CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. CONCLUSIONS: Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis.

A novel method for blood volume estimation using trivalent chromium in rabbit models.

BACKGROUND: Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. AIMS: The aim was to compare blood volume estimations using trivalent chromium [(51)Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). MATERIALS AND METHODS: Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of (51)Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using (51)Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using (51)Cr(III). RESULTS: The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using (51)Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using (51)Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). CONCLUSIONS: The estimation of blood volume using (51)Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using (51)Cr(III) to find its application in acute clinical settings.

Safety-related outcomes for patients with a tracheostomy and the use of flexible endoscopic evaluation of swallowing (FEES) for assessment and management of swallowing: A systematic review.

PURPOSE: The purpose of this systematic review was to examine safety-related outcomes for patients with tracheostomy after flexible endoscopic evaluation of swallowing (FEES) to assess and manage their swallow, when compared to other non-instrumental swallow assessments such as clinical swallowing examination (CSE) and/or a modified Evans blue dye test (MEBDT). METHOD: Three databases were searched for articles referring to safety-related outcome data for adults with a tracheostomy, who underwent FEES and CSE and/or MEBDT. Articles were screened using predefined inclusion/exclusion criteria. RESULT: The search strategy identified 2097 articles; following abstract and full-text screening, seven were included for review. The summary of evidence found low to very low certainty that FEES was associated with improved outcomes across swallow safety, physiological outcomes, tracheostomy cannulation duration, functional outcomes, and detection of upper airway pathologies. CONCLUSION: This systematic review demonstrated low to very low certainty evidence from seven heterogeneous studies with low sample sizes that incorporating FEES may be associated with improved safety-related outcomes. There is less evidence supporting the accuracy of other swallow assessments conducted at the point of care (i.e. CSE and MEBDT). Future research requires studies with larger sample sizes and routine reporting of safety-related outcomes with use of FEES.

Influence of Acoustic Parameters and Sonication Schemes on Transcranial Blood-Brain Barrier Disruption Induced by Pulsed Weakly Focused Ultrasound.

Pulsed ultrasound combined with microbubbles use can disrupt the blood-brain barrier (BBB) temporarily; this technique opens a temporal window to deliver large therapeutic molecules into brain tissue. There are published studies to discuss the efficacy and safety of the different ultrasound parameters, microbubble dosages and sizes, and sonication schemes on BBB disruption, but optimal the paradigm is still under investigation. Our study is aimed to investigate how different sonication parameters, time, and microbubble dose can affect BBB disruption, the dynamics of BBB disruption, and the efficacy of different sonication schemes on BBB disruption. Method: We used pulsed weakly focused ultrasound to open the BBB of C57/B6 mice. Evans blue dye (EBD) was used to determine the degree of BBB disruption. With a given acoustic pressure of 0.56 MPa and pulse repetitive frequency of 1 Hz, burst lengths of 10 ms to 50 ms, microbubbles of 100 µL/kg to 300 µL/kg, and sonication times of 60 s to 150 s were used to open the BBB for parameter study. Brain EBD accumulation was measured at 1, 4, and 24 h after sonication for the time-response relationship study; EBD of 100 mg/kg to 200 mg/kg was administered for the dose-response relationship study; EBD injection 0 to 6 h after sonication was performed for the BBB disruption dynamic study; brain EBD accumulation induced by one sonication and two sonications was investigated to study the effectiveness on BBB disruption; and a histology study was performed for brain tissue damage evaluation. Results: Pulsed weakly focused ultrasound opens the BBB extensively. Longer burst lengths and a larger microbubble dose result in a higher degree of BBB disruption; a sonication time longer than 60 s did not increase BBB disruption; brain EBD accumulation peaks 1 h after sonication and remains 81% of the peak level 24 h after sonication; the EBD dose administered correlates with brain EBD accumulation; BBB disruption decreases as time goes on after sonication and lasts for 6 h at least; and brain EBD accumulation induced by two sonication increases 74.8% of that induced by one sonication. There was limited adverse effects associated with sonication, including petechial hemorrhages and mild neuronal degeneration. Conclusions: BBB can be opened extensively and reversibly by pulsed weakly focused ultrasound with limited brain tissue damage. Since EBD combines with albumin in plasma to form a conjugate of 83 kDa, these results may simulate ultrasound-induced brain delivery of therapeutic molecules of this size scale. The result of our study may contribute to finding the optimal paradigm of focused ultrasound-induced BBB disruption.

Nano-catalytic behavior of highly efficient and regenerable mussel-inspired Fe3O4@CFR@GO and Fe3O4@CFR@TiO2 magnetic nanospheres in the reduction of Evans blue dye.

Fe3O4@catechol formaldehyde resin coated @Graphene Oxide nanocomposite (Fe3O4@CFR@GO) and Fe3O4@catechol formaldehyde resin coated @TiO2 (Fe3O4@CFR@TiO2) nanocomposite were fabricated by hydrothermal method. Particularly, catechol bunches on the highest layer of nanospheres to play a mussel-inspired chemistry to assist combined with graphene oxide (GO) to wrap the Fe3O4@ coated nanosphere. The prepared catalyst was proven to be very efficient with less than a minute and vey less dosage (15-17 mg) in the adsorptive degradation of Evans blue dye. The adsorptive degradation of Evans blue dye with Fe3O4@CFR@GO and Fe3O4@CFR@TiO2 nanocomposites are studied by several variables like the dye concentration, dosage, pH, contact time and temperature. It shows maximum adsorption capacity of 0.1435 mg/g (Fe3O4@CFR@GO) and 9.345 mg/g (Fe3O4@CFR@TiO2) nanocomposites. The equilibrium concentration and the adsorption capacity were evaluated using three different isothermal models. The kinetic study determined that Evans blue dye adsorption was in good analogy with the pseudo-first-order kinetic model.

Swallowing problems in children with a tracheostomy.

Children with a tracheostomy often present with swallowing disorders. Assessing the impact the presence of the tracheostomy tube has on swallowing function next to the underlying pathology can be very challenging. This article gives an overview of normal swallowing physiology and development, swallowing difficulties as encountered in various airway pathologies and addresses the mechanism by which the tracheostomy tube impacts swallowing. We discuss methods of investigating swallowing disorders and offer tools for management in everyday practice.

An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields.

The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 µs (1028 V/cm), 5-2-5 µs (721 V/cm), 10-1-10 µs (547 V/cm), 2-5-2 µs (1043 V/cm), and 5-5-5 µs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.

Barrier Effect of a New Topical Agent on Damaged Esophageal Mucosa: Experimental Study on an ex vivo Swine Model.

PURPOSE: AL2106 is a new medical device based on a mixture of chondroitin sulphate in a xyloglucan and glycerol solution made to maximize its bioadhesive capability to the esophageal mucosa. The aim of the present study was twofold to evaluate the AL2106 protective effect on the esophageal mucosa when exposed to an acidic solution mimicking gastric reflux and to assess the resilience of this effect to saline washing. MATERIALS AND METHODS: A porcine ex vivo model was used and the effects of the new medical device were compared to a sodium alginate suspension (SAS) already present on the market which was assumed as reference. Mucosal damage was induced in 19 porcine esophagi by perfusion with an acidic solution added with pepsin, and Evans blue dye (EBD) tissue uptake was used as an indicator of mucosal permeability. The EBD penetration, expressed as EBD µg/g of dry tissue, was assessed in specimens of untreated damaged mucosa and in specimens treated with AL2106 or SAS. The same evaluation was carried out after washing with normal saline. RESULTS: Both topical agents tested significantly reduced the EBD uptake by more than 60% (AL2106 8.4±4.5, SAS 3.6±2.7 vs control 23.2±13.1, p<0.01). The saline washing did not cause any significant reduction in the protective effect of AL2106 (8.6±5.9), while it significantly reduced that of SAS (5.9±4.3, p<0.05). CONCLUSION: The new AL2106 medical device showed a good barrier effect against a reflux-like damaging solution and preserved this effect after the mucosal washing test, thus suggesting its possible relevance for the treatment of gastroesophageal reflux disease.

Constitutive accessibility of circulating proteins to hippocampal neurons in physiologically normal rats.

INTRODUCTION: Although the hippocampus (HIP) is thought impermeable to blood-borne proteins because of the integrity of the blood-brain barrier (BBB), it was recently suggested to be susceptible to hydrophilic hormones. The present study determined the accessibility of blood-borne signal molecules such as hormones to hippocampal neurons in physiologically normal rats. METHODS: As a probe for accessibility, Evans blue dye (EB) that rapidly binds to albumin (Alb), which is impermeable to the BBB, was injected intravenously. To increase the vascular permeability of the BBB, a daily single administration of angiotensin II (Ang II) was applied intravenously for seven consecutive days. RESULTS: Fifteen minutes after the injection of EB, histological observation revealed that a number of neurons had entrapped and accumulated EB into their cell bodies in the hippocampal dentate gyrus in all rats. Of these, relatively large oval neurons (>15 µm) in the hilus and molecular layer showed parvalbumin immunopositivity, indicating they are GABAergic interneurons. The population of EB-accumulating neurons (approximately 10 µm) were localized in the inner margin of the granule cell layer, suggesting they were granule cells. However, the number of EB-positive neurons did not change in rats treated with Ang II compared with vehicle injection. CONCLUSIONS: These findings suggest an intriguing possibility that blood-derived proteins such as hormones have access to hippocampal neurons constitutively in the absence of stimuli that increase the vascular permeability of the BBB in a physiologically normal state.

Dietary Betaine Improves Intestinal Barrier Function and Ameliorates the Impact of Heat Stress in Multiple Vital Organs as Measured by Evans Blue Dye in Broiler Chickens.

In a 2 × 2 factorial design, 60 male Ross-308 broilers were fed either a control or 1 g/kg betaine diet and housed under thermoneutral (TN) or heat stress (HS) conditions. Broilers were acclimated to diets for 1 week under TN (25 °C), then either kept at TN or HS, where the temperature increased 8 h/day at 33 °C and 16 h/day at 25 °C for up to 10 days. Respiration rate (RR) was measured at four time points, and on each of 1, 2, 3, 7 and 10 days of HS, 12 broilers were injected with 0.5 mg/kg of Evans Blue Dye (EBD) solution to quantify regional changes in tissue damage. Betaine was quantified in tissues, and ileal damage was assessed via morphometry and transepithelial resistance (TER). Heat stress elevated RR (p < 0.001) and resulted in reduced villous height (p = 0.009) and TER (p < 0.001), while dietary betaine lowered RR during HS (p < 0.001), increased betaine distribution into tissues, and improved ileal villous height (p < 0.001) and TER (p = 0.006). Heat stress increased EBD in the muscle and kidney of chickens fed the control diet but not in those receiving betaine. Overall, these data indicate that supplemented betaine is distributed to vital organs and the gastrointestinal tract, where it is associated with improved tolerance of HS. Furthermore, EBD markers help reveal the effects of HS on organs dysfunction.

Carbogen inhalation opens the blood-brain barrier in rats without causing long-term metabolic or neurological deficit.

The blood-brain barrier (BBB) prevents many drugs from entering the brain. Yet, conventional methods that open the BBB are technically demanding, poorly reversible, and can be associated with long-term adverse effects. In comparison, carbogen, which is introduced nearly a century ago as a treatment for psychiatric disorders, is easy to administer and readily available to many labs and hospitals. Here, we show that carbogen inhalation opened the BBB in rats, as indicated by the extravasation of an intravenous protein tracer. When the tracer was injected immediately or hours after carbogen inhalation, less tracer was detected in the rat brains, suggesting at least partial reversibility of this response after carbogen exhalation. Despite marked increase in BBB permeability, inhalation of carbogen for 30-90 min had no acute effect on the level of neuroinflammation or apoptosis in the brain, and had no long-term effect on body weight, food intake, locomotor activity, or learning and memory performance. Our study demonstrated that carbogen inhalation is a safe method to open the BBB.

Interactive effects of As, Cd and Zn on their uptake and oxidative stress in As-hyperaccumulator Pteris vittata.

The effects of arsenic (As), cadmium (Cd) and zinc (Zn) on each other's uptake and oxidative stress in As-hyperaccumulator Pteris vittata were investigated. P. vittata plants were exposed to 50 µM As, Cd and/or Zn for 15 d in 0.2-strength Hoagland solution. When applied alone, P. vittata accumulated 185 mg kg-1 As, 164 mg kg-1 Cd and 327 mg kg-1 Zn in the fronds. While Cd and Zn did not impact each other's uptake, As affected Cd and Zn uptake. Whereas As decreased Zn uptake, Zn affected As speciation in P. vittata fronds, with more arsenate (AsV) than arsenite (AsIII) being present. At 50 µM As, 75 µM Zn increased As accumulation in P. vittata fronds by 10 folds to 2363 mg kg-1 compared to 50 µM Zn. Although AsV was the predominant As species in all tissues, Cd enhanced AsIII levels in the fronds but increased AsV in the roots. Co-exposure of Cd + Zn elevated oxidative stress basing on thiobarbituric acid reactive substances, H2O2 content, Evans blue dye uptake, membrane injury index and reactive oxygen species (ROS) relative to single metal. By lowering Cd and Zn concentrations in P. vittata fronds, As reduced the associated stress comparative to Cd or Zn treatment. The results enhance our understanding of the mechanisms underlying the interactions between As, Cd and Zn in As-hyperaccumulator P. vittata.

Temporal Characterization of Blood-Brain Barrier Disruption with High-Frequency Electroporation.

Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood-brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the temporal, high-frequency electroporation (HFE)-mediated BBBD in an in vivo healthy rat brain model. 40 male Fisher rats underwent HFE treatment; two blunt tipped monopolar electrodes were advanced into the brain and 200 bursts of HFE were delivered at a voltage-to-distance ratio of 600 V/cm. BBBD was verified with contrast enhanced T1W MRI (gadopentetate dimeglumine) and pathologically (Evans blue dye) at time points of 1, 24, 48, 72, and 96 h after HFE. Contrast enhanced T1W scans demonstrated BBBD for 1 to 72 h after HFE but intact BBB at 96 h. Histologically, tissue damage was restricted to electrode insertion tracks. BBBD was induced with minimal muscle contractions and minimal cell death attributed to HFE. Numerical modeling indicated that brief BBBD was induced with low magnitude electric fields, and BBBD duration increased with field strength. These data suggest the spatiotemporal characteristics of HFE-mediated BBBD may be modulated with the locally applied electric field.

Swallowing problems in children with a tracheostomy tube.

INTRODUCTION: Swallowing problems in children with a tracheostomy tube seem to be a common problem, although exact prevalence is not known. The aim of this study is to identify the prevalence and type of swallowing problems in children with a tracheostomy tube. METHODS: We retrospectively included 44 children having a tracheostomy tube at Erasmus MC-Sophia Children's hospital. Assessment by a specialized speech and language therapist, the Modified Evans Blue Dye test, Video Fluoroscopic Swallowing Study and a Fiber-optic Endoscopic Evaluation of Swallowing were reviewed with regard to the different phases of swallowing, in particular signs of aspiration. RESULTS: In our cohort, 31 (70%) children with a tracheostomy tube presented with problems in the oral and/or the pharyngeal phase of swallowing. Overall 19 (43%) children aspirated. CONCLUSIONS: The majority of children with a tracheostomy tube have swallowing problems in the different swallowing phases with a high risk for aspiration.