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Prcis: Femtosecond laser-assisted cataract surgery (FLACS) leads to an increase in intraocular pressure (IOP) during the procedure and subsequent IOP reduction after surgery, with greater magnitude in eyes with higher preoperative IOP., Purpose: To evaluate the effect of FLACS using the LDVZ8 laser on IOP during and after surgery, and to compare the IOP-lowering effect of FLACS and conventional phacoemulsification cataract surgery (CPCS)., Patients and Methods: This prospective cohort study enrolled 395 healthy eyes (395 patients) scheduled for FLACS (n=245) and CPCS (n=150). FLACS was performed using the LDVZ8 laser. During FLACS, IOP was assessed before and immediately after docking. IOP reduction during a 6-month postoperative period was evaluated following FLACS and CPCS. Multivariate analyses were performed., Results: The mean IOP increase after docking was 2.3±4.1 mm Hg ( P <0.0001); the maximum increase was 17.6 mm Hg, peak of 38 mm Hg. Sixty-one eyes (25.1%) demonstrated an increase of ≥5 mm Hg and 10 (3.7%) showed an increase of ≥10 mm Hg; predocking IOP was associated with an IOP increase of ≥5 mm Hg ( P =0.029). IOP reduction over 6 months postsurgery was similar for FLACS and CPCS ( P >0.05), -1.33±3.12 mm Hg for FLACS ( P <0.001) and -1.4±2.87 mm Hg for CPCS ( P <0.001). Preoperative IOP correlated statistically significantly with IOP reduction in both FLACS (β -0.742, P <0.001) and CPCS (β -0.743, P <0.001)., Conclusions: Although the LDVZ8 laser procedure causes an increase in IOP in some healthy eyes, a subsequent decrease in IOP is observed after FLACS. The IOP-lowering effect of FLACS is similar to CPCS and tends to be more pronounced in eyes with higher preoperative IOP. Eyes with higher preoperative IOP are prone to IOP elevation during FLACS, a critical consideration for glaucoma patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Three-dimensional imaging has become an increasingly important component of orthodontics. Associated with this, however, is a higher radiation exposure for patients. New cone-beam computed tomography (CBCT) devices have been developed that can provide low-dose CBCT (LD-CBCT). We hypothesized that LD-CBCT is as precise and reproducible as standard high-dose CBCT (HD-CBCT) in segmenting roots and crowns as well as measuring tooth length., Methods: HD-CBCT and LD-CBCT scans were taken of four human cadaveric heads. Thirty single-rooted teeth were segmented twice by one investigator. The length of each tooth was also measured. Lin's concordance correlation coefficient (CCC) was calculated to assess the agreement of HD-CBCT and LD-CBCT measurements and the intraclass correlation coefficient (ICC) was calculated to assess intrarater reliability. Analyses were supported by Bland-Altman plots., Results: Volume measurements obtained using HD-CBCT were significantly higher than those obtained using LD-CBCT (p < 0.001). CCC was 0.975 (95% confidence interval [CI] = 0.956-0.986) indicating excellent agreement between the two modalities. Intrarater reliability between the two sets of LD-CBCT and HD-CBCT volume measurements was excellent (ICC = 0.998, 95%CI = 0.995-0.999 [HD-CBCT], ICC = 0.997, 95%CI = 0.992-0.998 [LD-CBCT]). CCC for tooth length measurements was 0.991 (95% CI = 0.983-0.995), indicating excellent agreement between HD-CBCT and LD-CBCT. Intrarater reliabilities between the two sets of tooth length measurements were also excellent for both methods (ICC = 0.998, 95%CI = 0.995-0.999 [HD-CBCT], ICC = 0.997, 95%CI = 0.992-0.998 [LD-CBCT])., Conclusions: Within the limitations of this experimental setting, LD-CBCT is as valid as HD-CBCT for measuring tooth length. Regarding the volume differences, in vivo studies are required to determine their clinical relevance., (© 2024. The Author(s).)

In forensic casework, time since death (TSD) estimations may play a crucial role to establish chains of events as well as for alibi assessment in homicide cases. Classical TSD estimation relies on reasonably stable ambient temperatures and a correct documentation of ambient and rectal temperatures. This constancy is in some cases disturbed by post-discovery alterations of the crime scene, e.g. opening a window. In order to develop a better understanding of this alteration-based detrimental impact on TSD estimation as well as to identify feasible recommendations for casework, the present pilot study examined ambient temperature effects of different window opening scenarios regarding various time intervals (5 to 360 min) in a furnished 10 m 2 apartment during winter. In this context, in addition to the ambient temperature and thus the cooling rate of the room, re-approximation to initial room temperature, potential influences on a nomogram-based time since death estimation using a fictitious case, and the impact of the measurement height above the ground were investigated. Our data indicate a significant reduction of the mean temperature decrease rate after 15 min regardless of the remaining opening time and a correlation with the size of the respective opening surfaces. Re-approximation to initial room temperatures was observed with up to three times longer than the initial opening time. There was no evidence of a substantial advantage of temperature measurements above the level of the corpse (> 0.1 m). The limitations of the study and its applicability for forensic casework are critically reviewed., (© 2024. The Author(s).)

Background: The purpose of this study was to establish a standardized structured workflow to compare findings from high-resolution, optimized reconstructions from post-mortem computed tomography (pmCT) with autopsy results in the detection of fractures of the laryngohyoid complex in strangulation victims., Method: Forty-two strangulation cases were selected, and pmCT scans of the laryngohyoid complex were obtained. Both pmCT scans and autopsy reports were analyzed using a structured template and compared using Cohen's kappa coefficient (κ) and the McNemar test. The study also compared the prevalence of ossa sesamoidea and non-fusion of the major and minor horns of the hyoid bone between both diagnostic methods., Results: The detection of fractures showed a very good correlation between autopsy and pmCT results (κ = 0.905), with the McNemar test showing no statistically significant difference between the two methods. PmCT identified 28 sesamoid bones, 45 non-fusions of the major horns, and 47 non-fusions of the minor horns of the hyoid bone, compared to four, six, and zero, respectively, identified by autopsy ( p < 0.0001)., Conclusions: Autopsy and pmCT findings correlate well and can be used in a complementary manner. PmCT is superior to autopsy in identifying dislocations and detecting anatomical variations in the laryngohyoid complex, which can lead to misinterpretations during autopsy. Therefore, we do not advocate replacing autopsy with pmCT but propose using a structured workflow, including our standardized reporting template, for evaluating lesions in the laryngohyoid complex.

Importance: There are suggestions that school pressure may be stressful and a factor in child and adolescent mental health disturbances, but data about this association are scarce and inconclusive., Objective: To assess whether varying degrees of school interruption were associated with changes in emergency department (ED) psychiatric visits of children and adolescents before and after the COVID-19 outbreak., Design, Setting, and Participants: A cross-sectional observational study was conducted at 9 urban university hospitals in Italy. All ED visits from January 1, 2018, to December 31, 2021, for psychiatric reasons of patients younger than 18 years were examined for demographic characteristics and type of psychopathologic factors. Data analysis was conducted from July 1 to August 31, 2023., Exposure: The disruption in the usual succession of school and holiday periods brought on by the COVID-19 pandemic at different times and with various degrees of intensity., Main Outcomes and Measures: Total number of pediatric ED visits, psychiatric ED visits, and psychiatric ED visits categorized by specific reasons (eg, psychomotor agitation, suicide ideation [SI] or suicide attempt [SA], and eating disorders) on a weekly basis., Results: A total of 13 014 psychiatric ED visits (1.3% of all pediatric ED visits) were recorded (63.2% females; mean [SD] age, 13.8 [3.8] years). The number of ED psychiatric visits increased over time (incidence rate ratio [IRR], 1.19; 95% CI, 1.16-1.22 for each year). Significant increases in ED visits were observed for eating disorders (294.8%), SI (297.8%), and SA (249.1%). School opening, but not social lockdown restriction, was associated with an increase in the number of ED psychiatric visits (IRR, 1.29; 95% CI, 1.23-1.34), which was evident for females and for SI with SA. Socioeconomic status was associated with an increase in psychiatric visits for males (IRR, 1.12; 95% CI, 1.04-1.20) but not females (IRR, 1.04; 95% CI, 0.98-1.10)., Conclusions and Relevance: In this study, school opening was associated with an increased incidence of acute psychiatric emergencies among children and adolescents, suggesting that school can be a substantial source of stress with acute mental health implications.

Activatable microbubble contrast agents for contrast-enhanced ultrasound have a potential role for measuring physiologic and pathologic states in deep tissues, including tumor acidosis. In this study, we describe a novel observation of increased harmonic oscillation of phosphatidylcholine microbubbles (PC-MBs) in response to lower ambient pH using a clinical ultrasound scanner. MB echogenicity and nonlinear echoes were monitored at neutral and acidic pH using B-mode and Cadence contrast pulse sequencing (CPS), a harmonic imaging technique at 7.0 and 1.5 MHz. A 3-fold increase in harmonic signal intensity was observed when the pH of PC-MB suspensions was decreased from 7.4 to 5.5 to mimic normal and pathophysiological levels that can be encountered in vivo . This pH-mediated activation is tunable based on the chemical structure and length of phospholipids composing the MB shell. It is also reliant on the presence of phosphate groups, as the use of lipids without phosphate instead of phospholipids completely abrogated this phenomenon. The increased harmonic signal likely is the result of increased MB oscillation caused by a decrease of the interfacial tension induced at a lower pH, altering the lipid conformation. While relative signal changes are interpreted clinically as mostly related to blood flow, pH effects could be significant contributors, particularly when imaging tumors. While our observation can be used clinically, it requires further research to isolate the effect of pH from other variables. These findings could pave the way toward for the development of new smart ultrasound contrast agents that expand the clinical utility of contrast-enhanced ultrasound.

Objective: The current study explores whether there is a clinically relevant distinction in the measurement of marginal bone loss when comparing high-dose (HD) versus low-dose (LD) cone beam computed tomography (CBCT) protocols in small and large acquisition volumes.  Material and Methods: CBCTs of four human cadaveric preparates were taken in HD and LD mode in two different fields of view 8 × 8 cm2 (LV) and 5 × 5 cm2 (SV). In total, 43 sites of 15 teeth were randomly chosen, and marginal bone loss was measured twice in all protocols at 43 sites of 15 teeth by one calibrated investigator. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were calculated to assess the extent of agreement of the measurements. Additionally, the rater scored the certainty in each of the measurements., Results: For HD-CBCT CCC of measurements obtained using SV versus LV was 0.991. CCC of measurements obtained using SV versus LV of LD-CBCT was 0.963. Both CCC values indicated excellent agreement between the two volumes in both protocols.  CCC also indicated high intramodality correlation between HD-CBCT and LD-CBCT independent of the acquisition volume (0.963 - 0.992). Bland-Altman plots also indicated no substantial differences. Results of certainty scoring showed significant differences (p = 0.004 (LV), p < 0.001(SV)) between the LD and HD-CBCT., Conclusions: Accuracy of measurements of bone loss shows no clinical noticeable effects depending on the CBCT volume in this ex vivo study. There appears to be no relevant advantage of SV over LV, neither in HD-CBCT nor in LD-CBCT and additionally no relevant advantage of HD versus LD in visualizing marginal bone loss.

Objective: We have previously determined that direct formulation of a phospholipid-based perfluorobutane (PFB) emulsion using high-pressure homogenization produces monodispersed PFB nanodroplets (NDs) with relatively few non-PFB-filled NDs. In this article, we describe a simpler strategy to reproducibly formulate highly concentrated superheated PFB NDs using a probe sonicator, a more widely available tool., Methods: Similar to the homogenization technique, sonicating at low power a solution of phospholipids with condensed PFB at -10°C consistently yields NDs with an encapsulation efficiency close to 100% and very few non-PFB-filled particles., Results: The PFB emulsion is stable with absence of spontaneous vaporization at 37°C and for more than 14 d when frozen or refrigerated and for 3 d at 25°C. Acoustic droplet vaporization (ADV) occurred at a mechanical index >0.5 and continued to increase thereafter. The ADV threshold was similar for freshly made or frozen emulsion after thawing. In contrast to the microbubble (MB) condensation method, in which the ratio of non-PFB-filled to PFB-filled is 2000:1, particularly if MBs are not washed after formulation, nearly 94% of particles produced by direct sonication are PFB filled., Conclusion: PFB NDs can be manufactured with high yield, stability and reproducibility using a probe sonicator that is available in many laboratories. Their ease of manufacture could spark discoveries into highly impactful ND-based diagnostic and therapeutic applications., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Cellulose, as a naturally abundant and biocompatible material, is still gaining interest due to its high potential for functionalization. This makes cellulose a promising candidate for replacing plastics. Understanding how cellulose interacts with various additives is crucial for creating composite materials with diverse properties, as it is the case for plastics. In addition, the mechanical properties of the composite materials are assumed to be related to the mobility of the additives against the cellulose. Using a well-defined cellulose model surface (CMS), we aim to understand the adsorption and desorption of two polymeric particles (core-shell particles and microgels) to/from the cellulose surface. The nanomechanics of particles and CMS are quantified by indentation measurements with an atomic force microscope (AFM). AFM topography measurements quantified particle adsorption and desorption on the CMS, while peak force AFM measurements determined the force needed to move individual particles. Both particles and the CMS exhibited pH-dependent charge behavior, allowing a tunable interaction between them. Particle adsorption was irreversible and driven by electrostatic forces. In contrast, desorption and particle mobility forces are dominated by structural morphology. In addition, we found that an annealing procedure consisting of swelling/drying cycles significantly increased the adhesion strength of both particles. Using the data, we achieve a deeper understanding of the interaction of cellulose with polymeric particles, with the potential to advance the development of functional materials and contribute to various fields, including smart packaging, sensors, and biomedical applications.

As the population ages, the prevalence of heart failure and individuals wearing an implanted cardiac device is increasing. The combination of different underlying pathophysiologies and (the combination of) implanted cardiac devices can become a challenge with regard to the determination of cause and manner of death in such individuals. Additionally, heart disease is frequently associated with mental disease, ranging from anxiety and depression to suicidality and suicide (attempts). At the same time, the correct diagnosis of cause and manner of death is the basis for quality assurance, further therapeutic advances, legal safety, and suicide prevention. By that, an interdisciplinary field between legal medicine, clinicians, and law enforcement opens up. In this field, the different participants can simultaneously benefit from and need each other. For example, legal medicine experts need investigatory results and clinical expertise for the interpretation of readout data of implanted cardiac devices in order to correctly determine the cause of death. A correctly determined cause of death can assist law enforcement and help clinicians to further improve various therapeutic approaches based on correct mortality data collection. In addition, it is the basis for identification of suicides of device carriers, allowing psychological and psychiatric experts to better understand the burden of mental disease in this particular cohort. Against this interdisciplinary background, this manuscript summarizes information about psychiatric comorbidities and suicidality while being on a device. Thereby, basic information on complications and malfunctions of implanted cardiac devices, device-associated deaths with particular emphasis on device manipulation is displayed as basic information needed for correct determination of the cause of death. Also, legal and ethical issues in this field are outlined. The final result is a proposal of an interdisciplinary assessment workflow for a conjoint approach to improve the diagnosis of deaths associated with implanted cardiac devices. It will allow for a differentiation between an individual who died with or due to the device., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Federspiel, Potente, Abeln, Hennemann, Heinbuch, Burkhard, Richl, Kettner, Lux, Schmidt, Verhoff and Ramsthaler.)

Activating patients' immune cells, either by reengineering them or treating them with bioactive molecules, has been a breakthrough in the field of immunotherapy and has revolutionized treatment, especially against cancer. As immune cells naturally home to tumors or injured tissues, labeling such cells holds promise for non-invasive tracking and biologic manipulation. Our study demonstrates that macrophages loaded with extremely low boiling point perfluorocarbon nanodroplets not only survive ultrasound-induced phase change but also maintain their phagocytic function. Unlike observations made when using higher boiling point perfluorocarbon nanodroplets, our results show that phase change occurs intracellularly at a low mechanical index using a clinical scanner operating within the energy limit set by the Food and Drug Administration (FDA). After nanodroplet-loaded macrophages were given intravenously to nude rats, they were invisible in the liver when imaged at a very low mechanical index using a clinical ultrasound scanner. They became visible when power was increased but still within the FDA limits up to 8 h after administration. The acoustic labeling and in vivo detection of macrophages using a clinical ultrasound scanner represent a paradigm shift in the field of cell tracking and pave the way for potential therapeutic strategies in the clinical setting.

In the frame of an experimental setting, the formation of round-shaped compounded glass fragments on the exit site after gunshots through a windshield was examined. For that purpose, a 9 × 19 mm pistol (HK P30) and two different cartridges containing (a) a full metal jacketed round-nosed projectile and (b) a deformation projectile were used. On the basis of 52 gunshots, the morphology, impact angles and terminal ballistics of occurring compounded glass fragments were examined. The results showed that the compounded glass fragments' morphology allowed for the differentiation of two used projectiles. Fragments were able to cause round-shaped defects in a single cotton layer (T-shirt) with subsequent penetration of up to 2.4 cm into ballistic gelatin (10%, 4 °C). As a function of the projectile type, the compounded glass fragments showed different reproducible impact angles that differed notably from the known conical pattern of expelled glass fragments after bullet penetration. These findings might help to explain the atypical morphology of gunshot wounds with laminated glass as an intermediate target and prevent possible misinterpretations when reconstructing the sequence of events., (© 2022. The Author(s).)

Three intermediate-range shots from a Browning, model 1955, 7.65 mm caliber, pistol were fired from the driver's seat of a car at a woman in the passenger seat. She sustained three wounds: An, ultimately fatal, penetrating head wound, a graze wound across her forehead, and a tangential, perforating, wound, with bullet entry over the medial sternum and exit through the right flank. Neither postmortem CT nor forensic autopsy discovered bony thoracic injuries or perforations of the thoracoabdominal cavities. There was pulmonary contusion in the medial lobe of the right lung and hemorrhage in the adipose tissue around the right kidney. The tangential bullet had left an almost 40-cm-long wound channel through a pronounced layer of subcutaneous fat. Based on 3D reconstructed CT-data determinations, a straight bullet trajectory between entry and exit wounds would have traversed the abdominothoracic cavities, right lung, and liver. The actual trajectory, however, described a prominent curve, without signs of deflection by bone. Postulated explanations for this unusual bullet track are that the woman was twisting her body in a dynamic scene when the bullet struck; further, due to its shallow angle of incidence on the skin, the bullet was deflected to an intracutaneous path. Additionally, soft tissue resistance may have caused the bullet to yaw. Caution should, thus, be exercised when reconstructing bullet trajectories solely from entry and exist wounds, also for bullet wounds through basically homogenous soft tissues., (© 2022. The Author(s).)

Purpose: Identifying buccal and oral bone as an important supporting periodontal structure for teeth provides important information for treatment planning in periodontics and orthodontics. This study aims to add evidence to the knowledge of preciseness of cone beam computed tomography (CBCT) measurements of the vertical dimension of buccal and oral bone. The hypothesis is that CBCT is an accurate and reliable method to measure vertical vestibular and oral bone loss., Methods: The amount of vertical buccal and oral bone loss (bl) of 260 sites of 10 human cadavers was investigated clinically and radiographically by CBCT. Radiographic measurements were rated by two blinded raters. Measurements and the corresponding differences between clinical and radiological findings are described by medians and quartiles (Q1-Q3). For statistical analysis, Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were calculated., Results: The CCC between the raters was 0.994 (95% confidence interval 0.992-0.995). The median bone loss (bl) distance from the cementoenamel junction (CEJ) to the bony defect (BD) was 3.5 mm (range 3-5 mm). The median bl measured in the CBCT was 3.8 mm (range 3.1-4.8 mm). The median difference of the 2 measurements for all sites included in the study (N = 260) was -0.2 mm (-0.7 to 0.3 mm)., Conclusions: CBCT seems to be an accurate and highly reliable method to detect and describe vertical buccal and oral bone loss. It could improve planning and prediction for successful combined periodontal and orthodontic therapies., (© 2021. The Author(s).)

Shifting realities across the world have emphasized the need to change early childhood systems thinking. Specifically, a quality early childhood workforce was in high demand before the COVID-19 pandemic and will continue to be in demand until sustainable recruitment and retention efforts are achieved. Encouraging more professionals to enter and stay in the field of early childhood education involves building an understanding of the current workforce through analyzing the influence of age, role, education, wages, and access to incentives on career motivation. In this case study, a rich description of Montana's early childhood workforce is presented along with recommendations to strengthen the state's early childhood workforce systems. Results of survey and focus group data collection and analysis confirmed the pervasive compensation disparity that exists in the early childhood workforce and revealed the need for financial incentives to pursue and attain higher education degrees to help ensure the delivery of quality early childhood education. Specific recommendations for policy change include sharing the data across other state systems and with other nations for the purpose of supporting the growth and development of the early childhood workforce in the United States and beyond., Supplementary Information: The online version contains supplementary material available at 10.1007/s10643-022-01308-3., Competing Interests: Conflict of interestThe authors have no funding or conflicts of interest to disclose., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Introduction: Multiple cardiovascular conditions can lead to unexpected fatality, which is defined as sudden cardiac death. One of these potentially underlying conditions is aortic regurgitation, which can be caused by discrete changes of the geometry of the proximal aorta. To analyze aortic valve competency and furthermore to elucidate underlying pathological alterations of the coronary arteries and the vasa vasorum a perfusion method to simulate a diastolic state was designed., Material and Methods: A postmortem approach with retrograde perfusion of the ascending aorta with methylene blue was applied to three bodies. The procedure comprised cannulation of the brachiocephalic trunk, clamping of the aortic arch between brachiocephalic trunk and left carotid artery, infusion of 250 ml of methylene blue, and optical clearing of the superficial tissue layers after perfusion. Organs were examined directly following perfusion and after optical clearing., Results: Assessment and visualization of aortic valve competency and the vasa vasorum were possible in all three instances. Visualization of the coronary perfusion was impaired by postmortem thrombus formation. Optical clearing did not provide additional information., Discussion: The method presented here is a time- and cost-efficient way of visualizing aortic valve competency and the vasa vasorum. The visualization of the vasa vasorum highlights the potential of this method in basic research on diseases of the great arteries and coronaries. However, for a time-efficient functional analysis of the coronaries, other methods must be applied., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial for priming adaptive antitumour immunity through antigen-presenting cells (APCs). Natural agonists, such as cyclic dinucleotides (CDNs), activate the cGAS-STING pathway, but their clinical translation is impeded by poor cytosolic entry and serum stability, low specificity and rapid tissue clearance. Here we developed an ultrasound (US)-guided cancer immunotherapy platform using nanocomplexes composed of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) electrostatically bound to biocompatible branched cationic biopolymers that are conjugated onto APC-targeting microbubbles (MBs). The nanocomplex-conjugated MBs engaged with APCs and efficiently delivered cGAMP into the cytosol via sonoporation, resulting in activation of cGAS-STING and downstream proinflammatory pathways that efficiently prime antigen-specific T cells. This bridging of innate and adaptive immunity inhibited tumour growth in both localized and metastatic murine cancer models. Our findings demonstrate that targeted local activation of STING in APCs under spatiotemporal US stimulation results in systemic antitumour immunity and improves the therapeutic efficacy of checkpoint blockade, thus paving the way towards novel image-guided strategies for targeted immunotherapy of cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The GI microbiome has not been characterized in dogs being medically managed for congenital portosystemic shunts (CPSS)., Objectives: To characterize the fecal microbiome in a population of dogs being medically managed for CPSS., Animals: 27 client-owned dogs., Methods: Prospective cohort study enrollment of fecal samples was performed with follow-up data collected retrospectively. The overall fecal dysbiosis index (DI) and individual bacterial abundances were determined using real-time qPCR. Medical management, clinical findings, clinicopathologic, and outcome variables were collected, and logistic regression analyses were performed to evaluate associations between these variables and overall DI and bacterial abundances. Numerical variables were evaluated with general linear models for normality and equal variance using Shapiro-Wilk test and Levene's test, respectively., Results: All dogs were administered a hepatic diet and lactulose, while antibiotics were used in 22 (81.5%) and acid suppressants in 7 (25.9%). Seventeen dogs (63.0%) had a DI >2. The median DI in this population was 3.02 (range 4.23-8.42), and the median DI in dogs receiving and not receiving antibiotics was 4.3 (range -4.23-8.42) and 1.52 (range -1.62-5.43), respectively. No significant association between any of the analyzed variables and the DI was identified. There was a significant association between the use of metronidazole and a larger abundance of E. coli ( p = 0.024)., Conclusions and Clinical Importance: Dysbiosis appears to be common in dogs that are being medically managed for CPSS, though the clinical significance remains unclear., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Squire, Lux, Tolbert, Lidbury, Sun and Suchodolski.)

Purpose: Ideal treatment timing in orthodontics is controversially discussed depending on the type and extent of the dysgnathia and malocclusion present, especially with regard to efficiency, patient burden and treatment efforts of early compared to regular or late treatment. This German clinical practice guideline aims to clarify, at which time points an orthodontic anomaly can be effectively treated and how treatment efficiency differs depending on treatment timing., Methods: A systematic literature search was performed in various guideline databases and databases PROSPERO, MEDLINE (PubMed), Cochrane Library, Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform according to a predefined PICO (Population, Intervention, Comparison and Outcomes with added qualitative search terms) search algorithm and strategy. Appraisal of scientific evidence of the individual studies checked for eligibility was carried out according to SIGN (Scottish Intercollegiate Guidelines Network), AMSTAR II (Assessing the Methodological Quality of Systemic Reviews), and AXIS (Appraisal Tool to Assess the Quality of Cross-sectional Studies) tools. Only controlled studies with a high, acceptable or moderate quality (and thus an acceptable risk of bias) were considered., Results: A total of 309 studies of over 11,000 sources screened were identified to be eligible for inclusion and critically appraised for study quality and risk-of-bias. No relevant guidelines relating to the aims of the present guideline were found. Elected delegates of in total 21 German scientific societies and organizations agreed upon a total of 19 evidence-based statements and recommendations based on a nominal consensus process., Conclusions: Although most malocclusions can be effectively treated both in the early, late mixed, and permanent dentition, evidence suggests that therapy of a pronounced skeletal or dental class II anomaly can be started early to reduce the risk of dental anterior tooth trauma, whereas in a moderate class II anomaly, therapy can preferably be carried out before or during the pubertal growth peak. Therapy of a skeletal or dental class III anomaly should be started early, as this also reduces the need for later surgery to correct the anomaly. The treatment of a pronounced skeletal or dental transverse anomaly should be started early in the upper jaw in order to utilize the high adaptivity of the maxillary structures in young patients., (© 2022. The Author(s).)

Purpose: Analysis of the influence of geranyl-geraniol (GG) addition on four bisphosphonate derivatives regarding their influence on cell viability and migration ability of bone metabolism and endothelial cells in vitro., Methods: Clodronate, pamidronate, ibandronate, and zoledronate were observed with and without GG addition, for their effect on human osteoblasts (HOB), normal human dermal fibroblasts (NHDF), human endothelial progenitor cells (EPC), and endothelial cells of the human umbilical cord (HUVEC) using migration-, MTT-, and colony-forming cell assays., Results: Data pointed to a depressing effect of all bisphosphonates on the migration ability of NHDF, EPC, and HOB. MTT assay demonstrated a decreased cell viability of HUVEC of all bisphosphonates in a 50 μM concentration and of NHDF when treated with 50 μM of clodronate, ibandronate, or zoledronate. Tested drugs showed a depressing effect on colony-forming potential of EPC even in a 5 μM concentration. GG addition demonstrated an attenuate impact on bisphosphonate effect on all primary cell cultures, respectively., Conclusion: In vitro comparison showed that the addition of GG weakens the effect of all bisphosphonates examined. It supports investigations that suggest GG to be able to prevent bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) in vivo. Future clinical trials may discover the local therapeutic use of GG for the prevention of BP-ONJ., (© 2021. The Author(s).)

Prcis: Femtosecond laser-assisted cataract surgery (FLACS) may cause thinning of the peripapillary retinal nerve fiber layer (pRNFL) in healthy eyes., Purpose: This prospective cohort study aimed to compare changes of pRNFL after FLACS using a liquid patient interface and conventional phacoemulsification cataract surgery (CPCS)., Patients and Methods: Included were 261 eyes (261 patients) with age-related cataracts and no ocular diseases scheduled either for FLACS (222 eyes) or CPCS (39 eyes). FLACS was performed using a Ziemer LDV Z8 laser. Average and quadrant pRNFL thickness was measured using optical coherence tomography before surgery and at 1, 3, and 6 months postoperatively. Postoperative changes in pRNFL thickness were compared within and between groups., Results: Mean quadrant and average pRNFL thicknesses significantly increased after both surgeries (P<0.001). However, pRNFL thinning occurred after FLACS and CPCS (17% vs. 5.1%, respectively, P>0.05). FLACS eyes showed a significant and stable decrease of average pRNFL thickness (P=0.057) and a gradual decrease in pRNFL thickness of all quadrants (P≤0.018). CPCS eyes showed an initial increase of pRNFL thickness, followed by a decrease only in the nasal quadrant and average pRNFL. Preoperative pRNFL thickness was associated with thinning of the temporal quadrant (P=0.04)., Conclusions: Both FLACS and CPCS demonstrated pRNFL thinning in some healthy eyes. Although the higher rate of pRNFL thinning after FLACS compared with CPCS lacked statistical significance, a consistent decrease in pRNFL thickness occurred in all quadrants and average pRNFL of FLACS eyes, suggesting that FLACS may lead to pRNFL thinning. Eyes with thinner preoperative pRNFL may be prone to temporal quadrant thinning after FLACS., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Different cone beam computed tomography (CBCT) protocols have shown promising results for imaging furcation defects. This study evaluates the suitability of low-dose (LD)-CBCT for this purpose. Fifty-nine furcation defects of nine upper and 16 lower molars in six human cadavers were measured by a high-dose (HD)-CBCT protocol, a LD-CBCT protocol, and a surgical protocol. HD-CBCT and LD-CBCT measurements were made twice by two investigators and were compared with the intrasurgical measurements, which served as the reference. Furcation defect volumes generated from HD-CBCT and LD-CBCT imaging were segmented by one rater. Cohen's kappa and intraclass correlation coefficient (ICC) values were calculated to determine intra- and interrater reliability. The level of significance was set at α = 0.05. In total, 59 furcation defects of nine upper and 16 lower human molars were assessed. Comparing CBCT furcation defect measurements with surgical measurements revealed a Cohen's kappa of 0.5975 (HD-and LD-CBCT), indicating moderate agreement. All furcation defects identified by HD-CBCT were also detected by LD-CBCT by both raters, resulting in a Cohen's kappa of 1. For interrater agreement, linear furcation defect measurements showed an ICC of 0.992 for HD-CBCT and 0.987 for LD-CBCT. The intrarater agreement was 0.994(r1)/0.992(r2) for HD-CBCT and 0.987(r1)/0.991(r2) for LD-CBCT. The intermodality agreement was 0.988(r1)/0.991(r2). Paired t-test showed no significant differences between HD-CBCT and LD-CBCT measurements. LD-CBCT is a precise and reliable method for detecting and measuring furcation defects in mandibular and maxillary molars in this experimental setting. It has the potential to improve treatment planning and treatment monitoring with a far lower radiation dose than conventional HD-CBCT., (© 2022. The Author(s).)

With the increasing use of CT and MRI for diagnostic imaging and planning of interventional procedures, it is important for veterinary radiologists to be familiar with variations in normal vascular anatomy and not mistake them for pathology. The arterial blood supply to the cranial abdominal viscera is provided by the celiac and the cranial mesenteric arteries. A common celiacomesenteric trunk (CMT) has been reported as a rare anatomical variant in dogs. The goals of this retrospective, observational, cross-sectional prevalence study were to determine the prevalence of a CMT in dogs with non-abdominal disease and compare it to the prevalence in dogs with portosystemic shunts (PSS). Magnetic resonance imaging studies of the thoracolumbar and lumbosacral spine in dogs that included the origin of the celiac and cranial mesenteric arteries and dual-phase CT angiography studies of the abdomen in dogs with portosystemic shunts were retrospectively reviewed by a veterinary student and a board-certified veterinary radiologist. The prevalence of a CMT was determined as the proportion of dogs diagnosed with this vascular anomaly in the MRI and CT group, respectively. Fisher's exact test was used to determine any association of a CMT with the concurrent presence of a PSS, sex, and breed size. A CMT was identified in seven of 606 (1.2%) MRI studies and in none of 47 abdominal CT studies. There was no association between the presence of a CMT and PSS (P = 1.000), sex (P = .4694), or breed size (P = 1.000). A CMT is a rare incidental finding in dogs., (© 2021 American College of Veterinary Radiology.)

Background: Despite best medical and surgical practice, some cases of chronic rhinosinusitis (CRS) can remain recalcitrant. Bacterial biofilms have been associated with the recalcitrance of sinonasal inflammation. Biofilms are highly resistant to commonly prescribed antibiotics. Accordingly, more effective antimicrobial treatment options are needed to treat refractory CRS. The aim of this study was to determine the in vitro efficacy of neutral electrolysed water (NEW) and povidone-iodine (PVI) against CRS-associated Staphylococcus aureus biofilms., Methods: Mature S. aureus biofilms were grown in a Centre for Disease Control (CDC) biofilm reactor. The antimicrobial activity of NEW, PVI and doxycycline was determined for both planktonic and biofilm cultures of a clinical S. aureus isolate using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays., Results: MICs and MBCs were determined for all antimicrobials. MBC values were similar to MICs for both antiseptics, but doxycycline MBCs were significantly higher than the associated MICs. Biofilms were highly resistant to NEW and doxycycline. The MBEC for doxycycline was between 500 and 1000 Â#181;g/mL. NEW was ineffective against biofilms and no MBEC could be determined. In contrast, a concentration of 10% of the commercial PVI solution (10 mg/mL PVI) led to effective eradication of mature biofilms., Conclusion: In this study, only PVI showed promising antibiofilm activity at physiological concentrations. The in vivo efficacy of PVI warrants further investigation of its potential as a treatment for recalcitrant CRS.

Within the scope of this technical report, the feasibility of indocyanine green (ICG) as a fluorescent agent for postmortem angiography of the heart is tested. The study included 4 deceased persons with no respective medical history of heart diseases. The basic patterns of findings in ICG fluorescence angiography associated with healthy hearts are presented. The method can easily be integrated into a workflow without restricting the macroscopic or histologic diagnostics. This paper represents the fundamental technical and analytical basis for upcoming studies concerning the possibilities and limitations of fluorescence angiography in the diagnosis of heart pathology., (© 2021. The Author(s).)

Perioperative administration of desmopressin has shown to significantly decrease rates of local recurrence and metastasis, and increase survival times in dogs with grade II and III mammary carcinomas. The objective of this study was to compare the oncologic outcome of cats with mammary carcinoma treated with bilateral mastectomy with or without perioperative administration of desmopressin. Medical records from nine veterinary institutions were searched to identify cats diagnosed with mammary carcinoma treated with bilateral mastectomy. Sixty cats treated with single-session or staged bilateral mastectomy were included. There were no significant differences in oncologic outcomes found between cats treated and not treated with desmopressin. No adverse effects were seen in any of the cats treated with perioperative desmopressin. Postoperative complications occurred in 18 cats (38.3%) treated with single-session bilateral mastectomy and in three cats (23.1%) treated with staged bilateral mastectomy (P = .48). Histologic grade and a modification of a proposed five-stage histologic staging system were both prognostic for disease-free interval. Incomplete histologic excision was associated with significantly increased rates of metastasis and tumour progression, and a shorter median survival time (MST). Cats that developed local recurrence also had a significantly shorter MST. The results of this study do not support the use of perioperative desmopressin to improve outcome when performing bilateral mastectomy for the treatment of mammary carcinoma in cats., (© 2020 John Wiley & Sons Ltd.)

Objective: By forcing closure of schools, curtailing outpatient services, and imposing strict social distancing, the COVID-19 pandemic has abruptly affected the daily life of millions worldwide, with still unclear consequences for mental health. This study aimed to evaluate if and how child and adolescent psychiatric visits to hospital emergency departments (EDs) changed during the pandemic lockdown, which started in Italy on February 24, 2020., Methods: We examined all ED visits by patients under 18 years of age in the 7 weeks prior to February 24, 2020, and in the subsequent 8 weeks of COVID-19 lockdown at two urban university hospitals, in Turin and Rome, Italy. ED visits during the corresponding periods of 2019 served as a comparison using Poisson regression modeling. The clinician's decision to hospitalize or discharge home the patient after the ED visit was examined as an index of clinical severity., Results: During the COVID-19 lockdown, there was a 72.0% decrease in the number of all pediatric ED visits (3,395) compared with the corresponding period in 2019 (12,128), with a 46.2% decrease in psychiatric visits (50 vs 93). The mean age of psychiatric patients was higher in the COVID-19 period (15.7 vs 14.1 years). No significant changes were found in hospitalization rate or in the prevalence distribution of the primary reason for the psychiatric ED visit (suicidality, anxiety/mood disorders, agitation)., Conclusions: In the first 8 weeks of the COVID-19-induced social lockdown, the number of child and adolescent psychiatric ED visits significantly decreased, with an increase in patient age. This decrease does not appear to be explained by severity-driven self-selection and might be due to a reduction in psychiatric emergencies or to the implementation of alternative ways of managing acute psychopathology., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

For tailored functionalization of cellulose based papers, the interaction between paper fibers and functional additives must be understood. Planar cellulose surfaces represent a suitable model system for studying the binding of additives. In this work, polyelectrolyte multilayers (PEMs) are prepared by alternating dip-coating of the negatively charged cellulose derivate carboxymethyl cellulose and a polycation, either polydiallyldimethylammonium chloride (PDADMAC) or chitosan (CHI). The parameters varied during PEM formation are the concentrations (0.1-5 g/L) and pH (pH = 2-6) of the dipping solutions. Both PEM systems grow exponentially, revealing a high mobility of the polyelectrolytes (PEs). The pH-tunable charge density leads to PEMs with different surface topographies. Quartz crystal microbalance experiments with dissipation monitoring (QCM-D) reveal the pronounced viscoelastic properties of the PEMs. Ellipsometry and atomic force microscopy (AFM) measurements show that the strong and highly charged polycation PDADMAC leads to the formation of smooth PEMs. The weak polycation CHI forms cellulose model surfaces with higher film thicknesses and a tunable roughness. Both PEM systems exhibit a high water uptake when exposed to a humid environment, with the PDADMAC/carboxymethyl cellulose (CMC) PEMs resulting in a water uptake up to 60% and CHI/CMC up to 20%. The resulting PEMs are water-stable, but water swellable model surfaces with a controllable roughness and topography.

Purpose: The COVID-19 pandemic and related lockdown measures drastically changed health care and emergency services utilization. This study evaluated trends in emergency department (ED) access for seizure-related reasons in the first 8 weeks of lockdown in Italy., Methods: All ED accesses of children (<14 years of age) at two university hospitals, in Turin and Rome, Italy, between January 6, 2020 and April 21, 2020, were examined and compared with the corresponding periods of 2019., Results: During the COVID-19 lockdown period (February 23-April 21, 2020), there was a 72 % decrease in all pediatric ED accesses over the corresponding 2019 period (n = 3,395 vs n = 12,128), with a 38 % decrease in seizure-related accesses (n = 41 vs n = 66). The observed decrease of seizure-related ED accesses was not accompanied by significant changes in age, sex, type of seizure, or hospitalization rate after the ED visit., Conclusion: The COVID-19 lockdown was accompanied by a sudden decrease in seizure-related hospital emergency visits. School closure, social distancing, reduced risk of infection, and increased parental supervision are some of the factors that might have contributed to the finding., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

In murine models, the expression of inducible nitric oxide synthase (iNOS) in myocardial infarction (MI) has been reported to be the result of tissue injury and inflammation. In the present study, mRNA expression of iNOS, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was investigated in postmortem human infarction hearts. Since HIF-1α is the inducible subunit of the transcription factor HIF-1, which regulates transcription of iNOS and VEGF, the interrelation between the three genes was observed, to examine the molecular processes during the emergence of MI. iNOS and VEGF mRNAs were found to be significantly upregulated in the affected regions of MI hearts in comparison to healthy controls. Upregulation of HIF-1α was also present but not significant. Correlation analysis of the three genes indicated a stronger and significant correlation between HIF-1α and iNOS mRNAs than between HIF-1α and VEGF. The results of the study revealed differences in the expression patterns of HIF-1 downstream targets. The stronger transcription of iNOS by HIF-1 in the affected regions of MI hearts may represent a pathological process, since no correlation of iNOS and HIF-1α mRNA was found in non-affected areas of MI hearts. Oxidative stress is considered to cause molecular changes in MI, leading to increased iNOS expression. Therefore, it may also represent a forensic marker for detection of early changes in heart tissue.

Mongolian spots (MS) are congenital dermal conditions resulting from neural crest-derived melanocytes migration to the skin during embryogenesis. MS incidences are highly variable in different populations. Morphologically, MS present as hyperpigmented maculae of varying size and form, ranging from round spots of 1 cm in diameter to extensive discolorations covering predominantly the lower back and buttocks. Due to their coloring, which is also dependent on the skin type, MS may mimic hematoma thus posing a challenge on the physician conducting examinations of children in cases of suspected child abuse. In the present study, MS incidences and distribution, as well as skin types, were documented in a collective of 253 children examined on the basis of suspected child abuse. From these data, a classification scheme was derived to document MS and to help identify cases with a need for recurrent examination for unambiguous interpretation of initial findings alongside the main decisive factors for re-examination such as general circumstances of the initial examination (e. g., experience of the examiner, lighting conditions) and given dermatological conditions of the patient (e. g., diaper rash).

The polyvinyl alcohol method (PVAL) is known as an effective technique to thoroughly collect traces of gunshot residue (GSR) from different surfaces, e.g., from hands or gunshot wounds. Despite obvious advantages over other methods using adhesive tapes, PVAL is still not widely accepted and applied in routine case work due to a required acquisition time of at least 15 to 20 min for a single shooting hand. In this study, the feasibility of a modified procedure taking 6 to 8 min per sample is tested within the frame of an experimental setting including (1) the collection of GSR from experimental gunshots with a semi-automatic pistol and lead-containing primer ammunition and (2) a simple experimental setting involving dry and moist artificial blood traces. In a third step, samples of four gun-associated suicide cases and one attempted suicide case were taken and analyzed. Furthermore, an exemplary implementation into a work flow of modern instrumental techniques of GSR analysis is presented.

Phase-change perfluorocarbon microdroplets were introduced over 2 decades ago to occlude downstream vessels in vivo. Interest in perfluorocarbon nanodroplets has recently increased to enable extravascular targeting, to rescue the weak ultrasound signal of perfluorocarbon droplets by converting them to microbubbles and to improve ultrasound-based therapy. Despite great scientific interest and advances, applications of phase-change perfluorocarbon agents have not reached clinical testing because of efficacy and safety concerns, some of which remain unexplained. Here, we report that the coexistence of perfluorocarbon droplets and microbubbles in blood, which is inevitable when droplets spontaneously or intentionally vaporize to form microbubbles, is a major contributor to the observed side effects. We develop the theory to explain why the coexistence of droplets and microbubbles results in microbubble inflation induced by perfluorocarbon transfer from droplets to adjacent microbubbles. We also present the experimental data showing up to 6 orders of magnitude microbubble volume expansion, which occludes a 200 μm tubing in the presence of perfluorocarbon nanodroplets. More importantly, we demonstrate that the rate of microbubble inflation and ultimate size can be controlled by manipulating formulation parameters to tailor the agent's design for the potential theranostic application while minimizing the risk to benefit ratio.

During evolution, chloroplasts, which originated by endosymbiosis of a prokaryotic ancestor of today's cyanobacteria with a eukaryotic host cell, were established as the site for photosynthesis. Therefore, chloroplast organelles are loaded with transition metals including iron, copper, and manganese, which are essential for photosynthetic electron transport due to their redox capacity. Although transport, storage, and cofactor-assembly of metal ions in chloroplasts are tightly controlled and crucial throughout plant growth and development, knowledge on the molecular nature of chloroplast metal-transport proteins is still fragmentary. Here, we characterized the soluble, ATP-binding ABC-transporter subunits ABCI10 and ABCI11 in Arabidopsis thaliana , which show similarities to components of prokaryotic, multisubunit ABC transporters. Both ABCI10 and ABCI11 proteins appear to be strongly attached to chloroplast-intrinsic membranes, most likely inner envelopes for ABCI10 and possibly plastoglobuli for ABCI11. Loss of ABCI10 and ABCI11 gene products in Arabidopsis leads to extremely dwarfed, albino plants showing impaired chloroplast biogenesis and deregulated metal homeostasis. Further, we identified the membrane-intrinsic protein ABCI12 as potential interaction partner for ABCI10 in the inner envelope. Our results suggest that ABCI12 inserts into the chloroplast inner envelope membrane most likely with five predicted α-helical transmembrane domains and represents the membrane-intrinsic subunit of a prokaryotic-type, energy-coupling factor (ECF) ABC-transporter complex. In bacteria, these multisubunit ECF importers are widely distributed for the uptake of nickel and cobalt metal ions as well as for import of vitamins and several other metabolites. Therefore, we propose that ABCI10 (as the ATPase A-subunit) and ABCI12 (as the membrane-intrinsic, energy-coupling T-subunit) are part of a novel, chloroplast envelope-localized, AAT energy-coupling module of a prokaryotic-type ECF transporter, most likely involved in metal ion uptake., (Copyright © 2019 Voith von Voithenberg, Park, Stübe, Lux, Lee and Philippar.)

Reactivation of fetal hemoglobin (HbF) is being pursued as a treatment strategy for hemoglobinopathies. Here, we evaluated the therapeutic potential of hematopoietic stem and progenitor cells (HSPCs) edited with the CRISPR-Cas9 nuclease platform to recapitulate naturally occurring mutations identified in individuals who express increased amounts of HbF, a condition known as hereditary persistence of HbF. CRISPR-Cas9 treatment and transplantation of HSPCs purified on the basis of surface expression of the CD34 receptor in a nonhuman primate (NHP) autologous transplantation model resulted in up to 30% engraftment of gene-edited cells for >1 year. Edited cells effectively and stably reactivated HbF, as evidenced by up to 18% HbF-expressing erythrocytes in peripheral blood. Similar results were obtained by editing highly enriched stem cells, defined by the markers CD34 + CD90 + CD45RA - , allowing for a 10-fold reduction in the number of transplanted target cells, thus considerably reducing the need for editing reagents. The frequency of engrafted, gene-edited cells persisting in vivo using this approach may be sufficient to ameliorate the phenotype for a number of genetic diseases., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Two geriatric (> 9 years old) dogs presented for vomiting, lethargy, and anorexia. Obstructive choledocholithiasis was diagnosed based on analysis of a serum biochemical analysis and abdominal radiographs and ultrasonography. In both dogs, choledocholiths were removed from the common bile duct via a choledochotomy without a cholecystectomy, and survival without recurrence occurred in both dogs for more than 1 year., Competing Interests: The authors declare that there are no conflicts of interesting regarding the publication of this article.

Perfluorocarbon emulsion nanodroplets containing iron oxide nanoparticles (IONPs) within their inner perfluorohexane (PFH) core were prepared to investigate potential use as an acoustically activatable ultrasound contrast agent, with the hypothesis that incorporation of IONPs into the fluorous phase of a liquid perfluorocarbon emulsion would potentiate acoustic vaporization. IONPs with an oleic acid (OA) hydrophobic coating were synthesized through chemical co-precipitation. To suspend IONP in PFH, OA was exchanged with perfluorononanoic acid (PFNA) via ligand exchange to yield fluorophilic PFNA-coated IONPs (PFNA-IONPs). Suspensions with various amounts of PFNA-IONPs (0-15% w/v) in PFH were emulsified in saline by sonication, using 5% (w/v) egg yolk phospholipid as an emulsifier. PFNA-IONPs were characterized with transmission electron microscopy (TEM), transmission electron cryomicroscopy (cryoTEM), and thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FTIR). IONP were between 5 and 10 nm in diameter as measured by electron microscopy, and hydrodynamic size of the PFH nanodroplets were 150 to 230 nm as measured by dynamic light scattering (DLS). Acoustic droplet vaporization of PFH nanodroplets (PFH-NDs) was induced using conversion pulses (100 cycle at 1.1 MHz and 50% duty cycle) provided by a focused ultrasound transducer, and formed microbubbles were imaged using a clinical ultrasound scanner. The acoustic pressure threshold needed for PFH-NDs vaporization decreased with increasing temperature and IONP content. PFH-NDs containing 5% w/v IONP converted to microbubbles at 42 °C at 2.18 MI, which is just above the exposure limits of 1.9 MI allowed by the FDA for clinical ultrasound scanners, whereas 10 and 15% emulsion vaporized at 1.87 and 1.24 MI, respectively. Furthermore, 5% IONP-loaded PFH-NDs injected intravenously into melanoma-bearing mice at a dose of 120 mg PFH/kg, converted into detectable microbubbles in vivo 5 h, but not shortly after injection, indicating that this technique detects NDs accumulated in tumors., (Copyright © 2019. Published by Elsevier B.V.)

Creativity is crucial to the capacity to do science well, to communicate it in compelling ways, and to enhance learning. Creativity can be both practiced and enhanced to strengthen conservation science professionals' efforts to address global environmental challenges. We explore how poetry is one creative approach that can further conservation scientists' engagement and learning. We draw on evidence from peer-reviewed literature to illustrate benefits of integrating science and poetry, and to ground our argument for the growth of a science-poetry community to help conservation scientists develop skills in creative practices as a component of professional development. We present examples from literature as well as two short poetry exercises for scientists to draw on when considering writing poetry, or deciding on forms of poetry to include, in their practice. Opportunity exists to grow science-poetry projects to further our understanding of what such initiatives can offer.

Brachycephalic airway syndrome (BAS) is characterized by increased upper airway resistance due to conformational abnormalities occurring in brachycephalic dogs (BD). In this prospective study, we evaluated pulse oximetry (SpO 2 ) and arterial blood gas values in 18 healthy BD and compared these values with those of 18 healthy mesocephalic and dolichocephalic dogs (MDD). All dogs were assigned a BAS score based on an owner questionnaire. Inclusion criteria included presentation to the hospital for a problem unrelated to the respiratory system and unremarkable blood analyses and physical examination. In awake dogs, SpO 2 values were obtained from a minimum of two sites. Dogs were then sedated, and SpO 2 values were obtained again concurrently with an arterial blood gas sample. The SpO 2 values were significantly lower in BD compared with MDD, but there were no statistically significant differences between BD and MDD for any arterial blood gas parameters. Based on the BAS score, BD who were moderately BAS-affected (n = 5), had significantly lower arterial saturation of hemoglobin with oxygen values on arterial blood gas when compared with MDD (n = 18). Although BD had statistically lower SpO 2 values than MDD, the mean SpO 2 values for both groups were within the normal range.

Hypercalcemia is a biochemical abnormality that, when left untreated, can lead to life-threatening complications including renal failure. Bisphosphonates are routinely used to treat hypercalcemia, but most literature on veterinary patients describes the use of pamidronate. This retrospective case series describes the use of zoledronate for treatment of hypercalcemia in four dogs. Information including signalment, clinical signs, treatment, and outcome was collected. All dogs showed a decrease in total and ionized calcium concentrations after treatment with zoledronate. All treatments of zoledronate administered were well tolerated, but a previously unreported local hypersensitivity reaction was observed in one dog. This report is the first to document the efficacy of zoledronate for treatment of hypercalcemia in dogs.

Ischemic heart failure is the leading cause of mortality worldwide. An early boost of intracardiac regenerative key mechanisms and angiogenetic niche signaling in cardiac mesenchymal stem cells (MSCs) could improve myocardial infarction (MI) healing. Epicardial erythropoietin (EPO; 300 U kg -1 ) was compared with intraperitoneal and intramyocardial EPO treatments after acute MI in rats ( n =156). Real-time PCR and confocal microscopy revealed that epicardial EPO treatment enhanced levels of intracardiac regenerative key indicators (SDF-1, CXCR4, CD34, Bcl-2, cyclin D1, Cdc2 and MMP2), induced transforming growth factor β (TGF-β)/WNT signaling in intramyocardial MSC niches through the direct activation of AKT and upregulation of upstream signals FOS and Fzd7, and augmented intracardiac mesenchymal proliferation 24 h after MI. Cardiac catheterization and tissue analysis showed superior cardiac functions, beneficial remodeling and increased capillary density 6 weeks after MI. Concomitant fluorescence-activated cell sorting, co-cultures with neonatal cardiomyocytes, angiogenesis assays, ELISA, western blotting and RAMAN spectroscopy demonstrated that EPO could promote cardiomyogenic differentiation that was specific of tissue origin and enhance paracrine angiogenetic activity in cardiac CD45 - CD44 + DDR2 + MSCs. Epicardial EPO delivery might be the optimal route for efficient upregulation of regenerative key signals after acute MI. Early EPO-mediated stimulation of mesenchymal proliferation, synergistic angiogenesis with cardiac MSCs and direct induction of TGF-β/WNT signaling in intramyocardial cardiac MSCs could initiate an accelerated healing process that enhances cardiac recovery., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma. DESIGN Retrospective case series. ANIMALS 107 client-owned cats. PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time. RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death. CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion may help to decrease the complication rate.

We describe the case of a man who was found with severe hypothermia and advanced myiasis involving five species of blow flies, which eventually led to a transtibial amputation of the man's right leg. A case of such a heavy and species-rich infestation with fly larvae in an urban environment is extraordinary and has, to our knowledge, never been described so far. Best practice in cases such as this one demands accurate species identification not only to ensure appropriate treatment and pest management but also, from a forensic point of view, to explore the possibility of third-party responsibility. The cooperation between physicians and forensic entomologists is highlighted.

Although myocarditis is caused by viral infections in about 50% of cases in European countries, various other causative agents are known. We report the case of a 51-year-old man who died several months after being diagnosed with asthma by his general practitioner. This diagnosis had been confirmed by a pulmonologist approximately 6 weeks before the man's death. To rule out the possibility of medical malpractice the prosecuting authority ordered a forensic autopsy. At autopsy macroscopic indicators for perimyocarditis and pneumonia were found. Microbiological and histological examination of tissue samples confirmed a diagnosis of Churg-Strauss syndrome, also known as Eosinophilic Granulomatosis with Polyangiitis (EGPA). The cause of death was determined to be cardiac involvement in Churg-Strauss syndrome. The presence of this disease also accounted for the man's recent medical history. There were no findings to indicate that a medical error had been made. The reported case illustrates why accessory histological and microbiological examinations should always be performed when macroscopic findings at autopsy suggest myocarditis. Determining the etiology of myocarditis is a necessary step to prevent overlooking rare diseases with inflammatory myocardial involvement, especially in the clarification of alleged medical malpractice.

The purpose of this in vitro study was to evaluate the effect of enamel sealants on bleaching of natural teeth by use of 40 % hydrogen peroxide in a dental surgery. The color stability of the results from bleaching was, furthermore, determined 10 months after the bleaching procedure. In a standardized setting, four sealants (Pro Seal ® , Light Bond™ Sealant, Protecto ® , and Clinpro™ XT Varnish) were applied to and removed from human teeth in accordance with the manufacturer's instructions. Natural teeth served as medium; half of the teeth were sealed and the others served as controls. Hydrogen peroxide gel (40 %; Opalescence Boost; Ultradent Products, South Jordan, UT, USA) was used as bleaching agent. Color measurement was performed with a spectroradiometer (Photoresearch PR670) before the bleaching process (T1) and 24 h (T2) and 10 months (T3) after bleaching. The spectroradiometer results were expressed by use of the Commission Internationale de l'Éclairage (CIE) L*a*b* color notation. The L*, a*, and b* values of the sealed and the unsealed surfaces were not significantly different at any time during the study (p > 0.05), irrespective of the sealant used. Ten months after the bleaching process, mean L*, a*, and b* values were lower than at 1-day post-bleaching; the mean value of ΔE between 1-day post-bleaching and 10 months post-bleaching was 2.46 (±3.1). The results of the study suggest that the effectiveness of professional tooth whitening is not appreciably affected by the application of the four sealants tested.

Microbubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>10 12 vs. NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable 10 NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were suficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells., Competing Interests: Conflicts of interest The authors confirm that there are no known conflicts of interest associated with this publication.

Emergency surgery was performed on a 6-year-old castrated male springer spaniel dog with evisceration of most of the small intestinal tract through the perineal region, secondary to a dog attack. This is the first report describing successful treatment of perineal evisceration secondary to dog attack at an untreated perineal hernia, employing abdominal and perineal approaches.

Aim: To evaluate the correlation between clinical and salivary microbial parameters during treatment with removable orthodontic appliances with or without use of fluoride mouth rinse., Materials and Methods: A group of 48 patients completed this randomized, controlled, parallel-group, clinical pilot study. 24 patients of the test group (TG) rinsed after tooth brushing with a fluoride mouth rinse (100 ppm AmF/150 ppm NaF) while 21 patients of the control group (CG) did not. Clinical parameters [Approximal Plaque Index (API), Papillary Bleeding Index (PBI)] as well as levels of salivary mutans streptococci (MS) and lactobacilli (LB) were assessed at baseline and after 3, 6, 9 and 12 months. Compliance was documented by participants. Appliance wear-times were estimated retrospectively by the patients. All participants received the same brushing instructions and were supplied with the same toothbrush/toothpaste., Results: A significant correlation of API values with MS levels (p=0.0003) or with LB levels (p=0.001) was observed. Furthermore, appliance wear-times were significantly associated with API values (p=0.02). The changes of MS or LB levels between beginning and end of the study did not differ significantly between study groups. The changes of the API scores showed slightly different median values (-3.5 in the TG vs. 0 in the CG), the difference, however, was not significant., Conclusions: The results emphasise the need for a careful monitoring of the oral hygiene status in patients with removable orthodontic appliances. Larger controlled clinical trials are necessary to investigate treatment options such as use of supplementary fluoride mouth rinse.