Efficient uptake of 85Sr and 60Co using fabricated inorganic sorbent for reducing radiation doses of simulated low-level waste.

The present study investigated the sorption behavior of 85Sr and 60Co radionuclides from aqueous solutions onto tin molybdate (SnMo) sorbent. SnMo has been synthesized using the precipitation method and was characterized using four analytical techniques including FT-IR, XRD, SEM, and XRF. The sorption studies applied on 85Sr and 60Co include the effect of shaking time, pH, concentration, and saturation capacity. The experimental data revealed that the sorption process was carried out after equilibrium time (180 min). The saturation capacity for 85Sr and 60Co is measured to be 58.1 and 52.2 mg g-1, respectively. The sorption behavior of studied radionuclides is dependent on pH values. Sorption kinetic better fit with the pseudo-second-order model. Furthermore, the sorption isotherm is better represented by the model proposed by Langmuir. The results of the desorption investigations indicated that the most effective eluents for achieving full recovery of investigated radionuclides were identified. Finally, the recycling results demonstrate the suitability of SnMo for affected sorbing of 85Sr and 60Co from aqueous solutions. All the obtained data clarify that the SnMo sorbent is an effective means of removing 85Sr and 60Co from liquid waste.

MRI scarcity in low- and middle-income countries.

Since the introduction of MRI as a sustainable diagnostic modality, global accessibility to its services has revealed a wide discrepancy between populations-leaving most of the population in LMICs without access to this important imaging modality. Several factors lead to the scarcity of MRI in LMICs; for example, inadequate infrastructure and the absence of a dedicated workforce are key factors in the scarcity observed. RAD-AID has contributed to the advancement of radiology globally by collaborating with our partners to make radiology more accessible for medically underserved communities. However, progress is slow and further investment is needed to ensure improved global access to MRI.

Reduction in Radiologist Interpretation Time of Serial CT and MR Imaging Findings with Deep Learning Identification of Relevant Priors, Series and Finding Locations.

RATIONALE AND OBJECTIVES: Finding comparison to relevant prior studies is a requisite component of the radiology workflow. The purpose of this study was to evaluate the impact of a deep learning tool simplifying this time-consuming task by automatically identifying and displaying the finding in relevant prior studies. MATERIALS AND METHODS: The algorithm pipeline used in this retrospective study, TimeLens (TL), is based on natural language processing and descriptor-based image-matching algorithms. The dataset used for testing comprised 3872 series of 246 radiology examinations from 75 patients (189 CTs, 95 MRIs). To ensure a comprehensive testing, five finding types frequently encountered in radiology practice were included: aortic aneurysm, intracranial aneurysm, kidney lesion, meningioma, and pulmonary nodule. After a standardized training session, nine radiologists from three university hospitals performed two reading sessions on a cloud-based evaluation platform resembling a standard RIS/PACS. The task was to measure the diameter of the finding-of-interest on two or more exams (a most recent and at least one prior exam): first without use of TL, and a second session at an interval of at least 21 days with the use of TL. All user actions were logged for each round, including time needed to measure the finding at all timepoints, number of mouse clicks, and mouse distance traveled. The effect of TL was evaluated in total, per finding type, per reader, per experience (resident vs. board-certified radiologist), and per modality. Mouse movement patterns were analyzed with heatmaps. To assess the effect of habituation to the cases, a third round of readings was performed without TL. RESULTS: Across scenarios, TL reduced the average time needed to assess a finding at all timepoints by 40.1% (107 vs. 65 seconds; p < 0.001). Largest accelerations were demonstrated for assessment of pulmonary nodules (-47.0%; p < 0.001). Less mouse clicks (-17.2%) were needed for finding evaluation with TL, and mouse distance traveled was reduced by 38.0%. Time needed to assess the findings increased from round 2 to round 3 (+27.6%; p < 0.001). Readers were able to measure a given finding in 94.4% of cases on the series initially proposed by TL as most relevant series for comparison. The heatmaps showed consistently simplified mouse movement patterns with TL. CONCLUSION: A deep learning tool significantly reduced both the amount of user interactions with the radiology image viewer and the time needed to assess findings of interest on cross-sectional imaging with relevant prior exams.

Sorption of cesium and gadolinium ions onto zirconium silico antimonate sorbent from aqueous solutions.

Using a batch equilibrium technique, the sorption of 137Cs and 153Gd onto synthesized zirconium silico antimonate (ZrSiSb) sorbent was examined. The new sorbent was prepared by precipitation technique and characterized by diverse analytical tools. The influence of shaking time, pH, metal ion concentrations, temperature, and a real sample was carried out. The data indicate that ZrSiSb has a very fast equilibrium time (30 min). The distribution coefficient values as a function of pH have sequence order; Cs(I) > Gd(III). The reaction kinetic obeys the pseudo-2nd-order model. The saturation capacity is 69.8 and 27.2 mg/g for Cs(I) and Gd(III), respectively. Equilibrium data were analyzed by various sorption isotherm models. Desorption studies showed that the best eluents for complete recovery (about 99%) of the selected ions are KCl for Cs(I) and CaCl2 for Gd(III). The sorption effectiveness of the new ZrSiSb to remove 137Cs and 153Gd from real low-level radioactive waste was examined. The results obtained showed that the prepared new composite can be applied as a hoped sorbent material to get rid of these radionuclides from different wastewaters.

Removal of 137Cs and 90Sr from simulated low-level radioactive waste using tin(IV) vanadate sorbent and its potential hazardous parameters.

This study is concerned with the sorption of 137Cs and/or 90Sr from low-level radioactive waste using tin(IV) vanadate (SnV) sorbent fabricated by the precipitation technique. The structure and properties of SnV were studied using different analytical tools such as X-ray diffraction, X-ray fluorescence, Fourier-transform infrared, and scanning electron microscopy. Batch technique was used to investigate the sorption behavior of SnV towards 137Cs and/or 90Sr considering the influence of independent parameters including pH of the solution, contact time, and initial metal ions concentrations in simulation studies using the γ emitting isotopes 134Cs and 85Sr as representatives of 137Cs and 90Sr, respectively. The sorption efficiency values of 70.3% and 92.2% were respectively obtained for 134Cs and 85Sr at optimum conditions (pH = 6, Ci = 100 mg/L, and time = 120 min). The amount sorbed (mg/g) increases by increasing pH and temperatures. The pseudo-2nd-order kinetic is a reaction command. Isotherm is more relevant to a Langmuir at different reaction temperatures. The sorption process was endothermic and spontaneous. The adsorption efficiency of the composite material was studied in removing both cesium and strontium nuclides from real low-level radioactive waste. This study showed that the new material can be used as a promising material to retain 137Cs and 90Sr from real radioactive waste.

Availability and Access to Medications for Puberty Induction and Maintenance in Adolescents with Hypogonadism in the Arab Region.

Background: Inducing puberty in hypogonadal patients enables achieving normal final adult height and healthy bone mass accrual and improves fertility potential. Reliable availability and access to medicines remain a challenge around the world, particularly in low-income countries. Aim: We aimed to describe the availability/access to medications used for inducing and maintaining puberty in centers within the Arab region. Method: A cross-sectional survey was conducted using a link to an online questionnaire, which was emailed to paediatric endocrinologists in the Arab region. The questionnaire consisted of three questions related to the availability of various forms of sex hormones. Results: 99 physicians from 16 countries participated in the study. The commonest available form of estrogen was conjugated estrogen (29% of centers), followed by ethinylestradiol (26%). Depot estradiol was available in 11 centers, while topical estrogen preparations of gel and patches were available in 6 and 10 centers, respectively. Medroxy progesterone was available in 26% of the centers, followed by norethisterone (24%). The combined forms of oral and transdermal patches of estrogen/progesterone were available in 35% and 9% of centers, respectively. Intramuscular testosterone (Sustanon) was the most commonly available preparation of testosterone, followed by the depot injection (Nebido), oral testosterone, and testosterone gel and cream. Conclusions: We report the first available data on medications used for puberty induction and maintenance in paediatric hypogonadism in the Arab region. Recommended preparations for this purpose are not widely available. Creating an essential list of medications used in paediatric endocrinology disorders might improve availability, access, and consequently practice.

Sorption of some radionuclides from liquid waste solutions using anionic clay hydrotalcite sorbent.

129I and 79Se are potentially important anionic radionuclides in safety assessments due to their high mobility, radiotoxicity, and long half life's (1.7 × 107 and 3.27 × 105 years, respectively). This study is interested in the sorption of 131I and 75Se radionuclides onto magnesium iron hydrotalcite (Mg/Fe HTlc). Mg/Fe HTlc was prepared by co-precipitation technique and characterized using different analytical tools such as FT-IR, XRD, XRF, TGA & DTA, SEM, and BET. Results obtained from this study showed that the adsorption process was a very fast equilibrium time (20 min). The distribution coefficient values as a function of pH have high separation factors for 131I at all different pHs. Reaction kinetic obeys the pseudo-second-order model. Maximum sorption capacity for 131I and 75Se has the values 21.45, and 9.25 mg/g respectively. Sorption isotherms are more relevant to a Langmuir isotherm. The % removal of 131I is decreased by increasing the concentration of competing species. The investigation evidenced that the prepared sorbent is suitable for the removal of 131I and 75Se from radioactive waste and could be considered potential material for purification of effluent polluted with these radionuclides.

Gamma radiation-induced polymerization of polyacrylic acid-dolomite composite and applications for removal of cesium, cobalt, and zirconium from aqueous solutions.

Gamma-irradiation initiated polymerization was utilized to prepare polyacrylic acid dolomite P(AA/D) nanocomposites. Different analytical techniques have been applied to investigate the structure of the new materials. XRD and TEM revealed the crystalline phase with an average particle size ranging from 2 to 4 nm. The ability of the prepared materials to remove cesium, cobalt, and zirconium ions from aqueous solutions was evaluated. The adsorption capacity of studied nanocomposites has an affinity sequence; Zr4+>Co2+≫Cs+ with values 77.8, 72.4, and 34.9 mg/g respectively. The effect of the interfering species reveals that the rate of adsorption of cesium, cobalt, and zirconium ions decreases with increasing concentrations of the interfering species. The investigation proved that the prepared nanocomposite is suitable material for the removal of the studied metals from aqueous solutions and could be considered as potential material for purification of effluent polluted with these metal ions.

Preparation, characterization, and applications of polyacrylonitrile/ball clay nanocomposite synthesized by gamma radiation.

Elimination of hazardous metals is of extreme worry for their toxicity at trace levels and accumulation in the biosystem. Polyacrylonitrile ball clay nanocomposite was prepared by gamma irradiation at 20 kGy. Different analytical tools were applied to prove morphology, functional groups, and chemical structure for prepared composite; SEM, TEM, IR, XRD, and XRF. From TEM and XRD data expose the studied composite has nanoscale and crystalline. The adsorption of Cs+, Co2+ and Fe3+ onto studied material took place after 24 h. Second order was preceded by the kinetic system. The capacity and effect of pH on kd reflect selectivity sequence; Co2+ > Fe3+ > > Cs+. Both Freundlich and Langmuir are applicable for investigated material. Finally, PAN/BC nanocomposite is suitable for the column technique.

Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with an estimated global prevalence of 1 in 4 individuals. Aberrant transcriptional control of gene expression is central to the pathophysiology of metabolic diseases. However, the molecular mechanisms leading to gene dysregulation are not well understood. Histone modifications play important roles in the control of transcription. Acetylation of histone 3 at lysine 9 (H3K9ac) is associated with transcriptional activity and is implicated in transcript elongation by controlling RNA polymerase II (RNAPII) pause-release. Hence, changes in this histone modification may shed information on novel pathways linking transcription control and metabolic dysfunction. Here, we carried out genome-wide analysis of H3K9ac in the liver of mice fed a control or a high-fat diet (an animal model of NAFLD), and asked whether this histone mark associates with changes in gene expression. We found that over 70% of RNAPII peaks in promoter-proximal regions overlapped with H3K9ac, consistent with a role of H3K9ac in the regulation of transcription. When comparing high-fat with control diet, approximately 17% of the differentially expressed genes were associated with changes in H3K9ac in their promoters, showing a strong correlation between changes in H3K9ac signal and gene expression. Overall, our data indicate that in response to a high-fat diet, dysregulated gene expression of a subset of genes may be attributable to changes in transcription elongation driven by H3K9ac. Our results point at an added mechanism of gene regulation that may be important in the development of metabolic diseases.

Pancreatic beta cell autophagy is impaired in type 1 diabetes.

AIMS/HYPOTHESIS: Pancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce reactive oxygen species to protect against apoptosis. While impaired islet autophagy has been demonstrated in human type 2 diabetes, it is unknown if islet autophagy is perturbed in the pathogenesis of type 1 diabetes. We hypothesised that beta cell autophagy is dysfunctional in type 1 diabetes, and that there is a progressive loss during early diabetes development. METHODS: Pancreases were collected from chloroquine-injected and non-injected non-obese diabetes-resistant (NOR) and non-obese diabetic (NOD) mice. Age- and BMI-matched pancreas tissue sections from human organ donors (N = 34) were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Tissue sections were stained with antibodies against proinsulin or insulin (beta cell markers), microtubule-associated protein 1 light chain 3 A/B (LC3A/B; autophagosome marker), lysosomal-associated membrane protein 1 (LAMP1; lysosome marker) and p62 (autophagy adaptor). Images collected on a scanning laser confocal microscope were analysed with CellProfiler and ImageJ. Secondary lysosomes and telolysosomes were assessed in electron micrographs of human pancreatic tissue sections (n = 12), and energy dispersive x-ray analysis was performed to assess distribution of elements (n = 5). RESULTS: We observed increased autophagosome numbers in islets of diabetic NOD mice (p = 0.008) and increased p62 in islets of both non-diabetic and diabetic NOD mice (p < 0.001) vs NOR mice. There was also a reduction in LC3-LAMP1 colocalisation in islets of diabetic NOD mice compared with both non-diabetic NOD (p < 0.001) and NOR mice (p < 0.001). Chloroquine elicited accumulation of autophagosomes in the islets of NOR (p = 0.003) and non-diabetic NOD mice (p < 0.001), but not in islets of diabetic NOD mice; and stimulated accumulation of p62 in NOR (p < 0.001), but not in NOD mice. We observed reduced LC3-LAMP1 colocalisation (p < 0.001) in residual beta cells of human donors with type 1 diabetes vs non-diabetic participants. We also observed reduced colocalisation of proinsulin with LAMP1 in donors with type 1 diabetes (p < 0.001). Electron microscopy also revealed accumulation of telolysosomes with nitrogen-dense rings in beta cells of autoantibody-positive donors (p = 0.002). CONCLUSIONS/INTERPRETATION: We provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes. We also document accumulation of telolysosomes with peripheral nitrogen in beta cells of autoantibody-positive donors, demonstrating altered lysosome content that may be associated with lysosome dysfunction before clinical hyperglycaemia. Similar macroautophagy impairments are present in the NOD mouse model of type 1 diabetes.

Providing insight into the incubation period of Mycobacterium ulcerans disease: two case reports.

BACKGROUND: Buruli ulcer caused by Mycobacterium ulcerans is endemic in parts of West Africa and is most prevalent among the 5-15 years age group; Buruli ulcer is uncommon among neonates. The mode of transmission and incubation period of Buruli ulcer are unknown. We report two cases of confirmed Buruli ulcer in human immunodeficiency virus-unexposed, vaginally delivered term neonates in Ghana. CASE PRESENTATION: Patient 1: Two weeks after hospital delivery, a baby born to natives of the Ashanti ethnic group of Ghana was noticed by her mother to have a papule with associated edema on the right anterior chest wall and neck that later ulcerated. There was no restriction of neck movements. The diagnosis of Buruli ulcer was confirmed on the basis of a swab sample that had a positive polymerase chain reaction result for the IS2404 repeat sequence of M. ulcerans. Patient 2: This patient, from the Ashanti ethnic group in Ghana, had the mother noticing a swelling in the baby's left gluteal region 4 days after birth. The lesion progressively increased in size to involve almost the entire left gluteal region. Around the same time, the mother noticed a second, smaller lesion on the forehead and left side of neck. The diagnosis of Buruli ulcer was confirmed by polymerase chain reaction when the child was aged 4 weeks. Both patients 1 and 2 were treated with oral rifampicin and clarithromycin at recommended doses for 8 weeks in addition to appropriate daily wound dressing, leading to complete healing. Our report details two cases of polymerase chain reaction-confirmed Buruli ulcer in children whose lesions appeared at ages 14 and 4 days, respectively. The mode of transmission of M. ulcerans infection is unknown, so the incubation period is difficult to estimate and is probably dependent on the infective dose and the age of exposure. In our study, lesions appeared 4 days after birth in patient 2. Unless the infection was acquired in utero, this would be the shortest incubation period ever recorded. CONCLUSIONS: Buruli ulcer should be included in the differential diagnosis of neonates who present with characteristic lesions. The incubation period of Buruli ulcer in neonates is probably shorter than is reported for adults.

A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo.

The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate ß-cell function in vivo. Specifically, we developed ß-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo ß-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study ß-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of ß-cell physiology in the endogenous islet niche.

Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet ß cells.

In type 1 diabetes, an autoimmune event increases oxidative stress in islet ß cells, giving rise to cellular dysfunction and apoptosis. Lipoxygenases are enzymes that catalyze the oxygenation of polyunsaturated fatty acids that can form lipid metabolites involved in several biological functions, including oxidative stress. 12-Lipoxygenase and 12/15-lipoxygenase are related but distinct enzymes that are expressed in pancreatic islets, but their relative contributions to oxidative stress in these regions are still being elucidated. In this study, we used mice with global genetic deletion of the genes encoding 12-lipoxygenase (arachidonate 12-lipoxygenase, 12S type [Alox12]) or 12/15-lipoxygenase (Alox15) to compare the influence of each gene deletion on ß cell function and survival in response to the ß cell toxin streptozotocin. Alox12-/- mice exhibited greater impairment in glucose tolerance following streptozotocin exposure than WT mice, whereas Alox15-/- mice were protected against dysglycemia. These changes were accompanied by evidence of islet oxidative stress in Alox12-/- mice and reduced oxidative stress in Alox15-/- mice, consistent with alterations in the expression of the antioxidant response enzymes in islets from these mice. Additionally, islets from Alox12-/- mice displayed a compensatory increase in Alox15 gene expression, and treatment of these mice with the 12/15-lipoxygenase inhibitor ML-351 rescued the dysglycemic phenotype. Collectively, these results indicate that Alox12 loss activates a compensatory increase in Alox15 that sensitizes mouse ß cells to oxidative stress.

Development of a new synthetic xerogel nanoparticles of silver and zinc oxide against causative agents of dermatophytoses.

BACKGROUND: Dermatophytes, which are the common causative agents of superficial infection on the human skin called dermatophytosis that can be treated by various antifungal drugs. Nanoparticles composed of such drugs have many benefits. A new form called xerogel of silver nanoparticles (Ag-NPs) and zinc oxide nanoparticles (ZnO-NPs) was prepared and tested against dermatophytes. METHODS: Xerogel consists of Ag-NPs and ZnO-NPs was prepared. Characteristics of chemical composition, surface morphology, and nanoparticle size were determined. Antidermatophytic action of prepared xerogel was investigated against Trichophyton mentagrophytes and Trichophyton verrucosum. RESULTS: The new preparation exhibited satisfactory character of xerogel nanoparticles. Trichophyton mentagrophytes showed more susceptibility to xerogel with lower minimum inhibitory concentration than T. verrucosum. CONCLUSIONS: Xerogel nanoparticles composed of Ag and ZnO were successfully prepared. They had antidermatophytic action in specific concentrations.

An In Vivo Zebrafish Model for Interrogating ROS-Mediated Pancreatic ß-Cell Injury, Response, and Prevention.

It is well known that a chronic state of elevated reactive oxygen species (ROS) in pancreatic ß-cells impairs their ability to release insulin in response to elevated plasma glucose. Moreover, at its extreme, unmitigated ROS drives regulated cell death. This dysfunctional state of ROS buildup can result both from genetic predisposition and environmental factors such as obesity and overnutrition. Importantly, excessive ROS buildup may underlie metabolic pathologies such as type 2 diabetes mellitus. The ability to monitor ROS dynamics in ß-cells in situ and to manipulate it via genetic, pharmacological, and environmental means would accelerate the development of novel therapeutics that could abate this pathology. Currently, there is a lack of models with these attributes that are available to the field. In this study, we use a zebrafish model to demonstrate that ROS can be generated in a ß-cell-specific manner using a hybrid chemical genetic approach. Using a transgenic nitroreductase-expressing zebrafish line, Tg(ins:Flag-NTR)s950 , treated with the prodrug metronidazole (MTZ), we found that ROS is rapidly and explicitly generated in ß-cells. Furthermore, the level of ROS generated was proportional to the dosage of prodrug added to the system. At high doses of MTZ, caspase 3 was rapidly cleaved, ß-cells underwent regulated cell death, and macrophages were recruited to the islet to phagocytose the debris. Based on our findings, we propose a model for the mechanism of NTR/MTZ action in transgenic eukaryotic cells and demonstrate the robust utility of this system to model ROS-related disease pathology.

Interleukin-6 Reduces ß-Cell Oxidative Stress by Linking Autophagy With the Antioxidant Response.

Production of reactive oxygen species (ROS) is a key instigator of ß-cell dysfunction in diabetes. The pleiotropic cytokine interleukin 6 (IL-6) has previously been linked to ß-cell autophagy but has not been studied in the context of ß-cell antioxidant response. We used a combination of animal models of diabetes and analysis of cultured human islets and rodent ß-cells to study how IL-6 influences antioxidant response. We show that IL-6 couples autophagy to antioxidant response and thereby reduces ROS in ß-cells and human islets. ß-Cell-specific loss of IL-6 signaling in vivo renders mice more susceptible to oxidative damage and cell death through the selective ß-cell toxins streptozotocin and alloxan. IL-6-driven ROS reduction is associated with an increase in the master antioxidant factor NRF2, which rapidly translocates to the mitochondria to decrease mitochondrial activity and stimulate mitophagy. IL-6 also initiates a robust transient decrease in cellular cAMP levels, likely contributing to the stimulation of mitophagy to mitigate ROS. Our findings suggest that coupling autophagy to antioxidant response in ß-cells leads to stress adaptation that can reduce cellular apoptosis. These findings have implications for ß-cell survival under diabetogenic conditions and present novel targets for therapeutic intervention.

Local mepivacaine before castration of horses under medetomidine isoflurane balanced anaesthesia is effective to reduce perioperative nociception and cytokine release.

BACKGROUND: In horses castration with primary intention healing is usually performed under balanced inhalation anaesthesia. To optimise analgesia, the use of local anaesthesia was tested. OBJECTIVES: To investigate the effect of local mepivacaine before castration with first intention healing under balanced medetomidine-isoflurane anaesthesia and flunixin meglumine, morphine analgesia on perioperative cytokine levels and pain in horses. STUDY DESIGN: Prospective blinded clinical study. METHODS: Twenty stallions were randomly assigned to control or mepivacaine groups. Flunixin meglumine was administered before sedation with medetomidine and followed by ketamine/diazepam intravenously (i.v.). Anaesthesia was maintained with isoflurane and 3.5 µg/kg per hour medetomidine. Mepivacaine horses were given mepivacaine 2% (3.5 mL SC, 1 mL/100 kg intrafunicularly, 2 mL/100 kg intratesticularly) on each side. For recovery, horses were given 2 µg/kg medetomidine i.v. and 0.1 mg/kg morphine i.m. and oral phenylbutazone (0.02 mg/kg q12h) for post-operative analgesia. One hour before premedication and 4, 8 and 24 h post-incision, pain was scored with three different pain scales (Equine Utrecht University Scale for Facial Assessment of Pain, Horse Grimace Scale, Equine Utrecht University Scale for Composite Pain Assessment) and plasma cytokines (interleukin-6 and tumour necrosis factor alpha) were measured. Data were analysed using repeated measures ANOVA, linear regression and unpaired t-test, significance level P≤0.05. RESULTS: Horses in both groups showed a significant increase in pain scores and cytokines compared to baseline. Post-operatively the mepivacaine group exhibited significantly lower pain scores and cytokine levels. Mean heart rate during anaesthesia was significantly lower in the mepivacaine group compared to control group (28.8 ± 1 and 33.2 ± 1.7 respectively). Otherwise there were no differences between the groups. MAIN LIMITATIONS: The decision to provide additional analgesia was based on the attending surgeon's assessment rather than a standardised rescue analgesia plan based on pain scores. The study was only conducted for 24 h post-castration and complications were not recorded. CONCLUSION: Local mepivacaine before castration with primary wound closure improved anaesthesia quality, attenuated post-operative increases in cytokines and reduced post-operative pain despite balanced anaesthesia with multimodal analgesia in control horses.

Inhibition of 12/15-Lipoxygenase Protects Against ß-Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes.

Islet ß-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-Lipoxygenase (12/15-LOX) is induced in ß-cells and macrophages during T1D and produces proinflammatory lipids and lipid peroxides that exacerbate ß-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling has suggested reduced promiscuity of ML351 compared with ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of proinflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced ß-cell oxidative stress, and preservation of ß-cell mass. In the nonobese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced ß-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in insulitis. The data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of ß-cell dysfunction and glycemic deterioration in models of T1D.

Extracorporeal shock wave lithotripsy (ESWL) monotherapy in children: Predictors of successful outcome.

INTRODUCTION AND OBJECTIVES: Although extracorporeal shock wave lithotripsy (ESWL) is the first choice for pediatric renal calculi <2 cm, the success rate after the first session is low. This is in contrast to other minimally invasive procedures like percutanous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS), which have higher rates of success. Therefore, the present study sought to identify predictors of success after one session of ESWL. PATIENTS AND METHODS: A prospective study including 100 children with renal stone burden <2 cm who underwent ESWL at the present institution. The success rate after the first session was analyzed, and the predictors of success were investigated. The success of ESWL monotherapy was defined by absence of any residual fragments after 3 months, on non-contrast spiral computerized tomography (NCCT) scan, without need of any additional intervention. RESULTS: Between January 2013 and October 2015, 100 children were treated with a Dornier Gemini lithotripter at the present institution. The mean patients age and stone size were 6 years (range: 1.8-14) and 13.1 mm (range: 6-20), respectively. After one session, 47% of patients showed complete clearance 3 months postoperative, those patients versus those who required an additional session or auxiliary procedures were younger in age, with smaller stone size and lower density. On multivariate analysis, only patient age was an independent predictor of success (odds ratio (OR) 0.9; P < 0.001). CONCLUSION: Patient's age was an important predictor for response after ESWL monotherapy: not only did children respond better than adults, but age was also an independent predictor within the pediatric group.