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Efficacy of novel albendazole salt formulations against secondary cystic echinococcosis in experimentally infected mice
Antimicrobial effects of nano titanium dioxide and disinfectants on maxillofacial silicones.
STATEMENT OF PROBLEM
Deficient hygiene of maxillofacial prostheses can be a source of infection, and various disinfectants, including nano-oxides, have been suggested for the disinfection of silicone prostheses. While maxillofacial silicones involving nano-oxides at different sizes and concentrations have been evaluated in terms of their mechanical and physical properties, reports are lacking on the antimicrobial effect of nano titanium dioxide (TiO2) incorporated into maxillofacial silicones contaminated by different biofilms.
PURPOSE
The purpose of this in vitro study was to evaluate the antimicrobial effects of 6 different disinfectants and nano TiO2 incorporation into maxillofacial silicone contaminated with Staphylococcus aureus, Escherichia coli, and Candida albicans biofilms.
MATERIAL AND METHODS
A total of 258 silicone specimens (129 pure silicones and 129 nano TiO2-incorporated silicones) were fabricated. Specimens in each silicone group (with or without nano TiO2) were divided into 7 disinfectant groups (control, 0.2% chlorhexidine gluconate, 4% chlorhexidine gluconate, 1% sodium hypochlorite, neutral soap, 100% white vinegar, and effervescent) in each biofilm group. Contaminated specimens were disinfected, and the suspension of each specimen was incubated at 37 °C for 24 hours. Proliferated colonies were recorded in colony-forming units per mL (CFU/mL). The differences in microbial levels among specimens were evaluated to test the effect of the type of silicone and the disinfectant (α=.05).
RESULTS
Significant difference was found among disinfectants regardless of the silicone type (P<.05). Nano TiO2 incorporation showed an antimicrobial effect on S aureus, E coli, and C albicans biofilms. Nano TiO2 incorporated silicone cleaned with 4% chlorhexidine gluconate had statistically less C albicans than pure silicone. Using white vinegar or 4% chlorhexidine gluconate led to no E coli on either silicone. Nano TiO2 incorporated silicone cleaned with effervescent had fewer S aureus or C albicans biofilms.
CONCLUSIONS
The tested disinfectants and nano TiO2 incorporation into silicone were effective against most of the microorganisms used in this study
Thrombectomy in Young Adults with Embolic Stroke of Undetermined Source: Analysis of the Young ESUS study.
OBJECTIVES
Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups.
MATERIALS AND METHODS
Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test.
RESULTS
Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients.
CONCLUSIONS
Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed
Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology.
BACKGROUND
Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood.
OBJECTIVES
We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.
METHODS
Following exposure to 20Gy of X-rays in a single fraction, neonatal rat ventricular cardiomyocytes (NRVCs) were analyzed 24 and 96h post-radiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration (APD) in both monolayers and single cells. Additionally, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and mRNA levels.
RESULTS
Following irradiation with 20Gy, NRVCs exhibited increased beat rate and conduction velocities 24 and 96h after treatment. mRNA and protein levels of ion channels were altered, with the most significant changes observed at the 96h-mark. Upregulation of Cacna1c (Cav1.2), Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1), Kcnj2 (Kir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 (RYR2) and Slc8a1 (NCX) expression and altered properties 96h post-treatment. Fibroblast and myofibroblast levels remained unchanged.
CONCLUSIONS
CSBRT modulates expression of various ion channels, calcium handling proteins, and gap-junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed following cSBRT
Refining Treatment Planning in STereotactic Arrhythmia Radioablation (STAR): Benchmark Results and Consensus Statement from the STOPSTORM.eu Consortium.
BACKGROUND AND PURPOSE
STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia (VT). However, clinical data is scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization.
METHODS
Planning target volumes (PTV) overlapping extra-cardiac organs-at-risk and/or cardiac substructures were generated for three STAR cases. Participating centers were asked to create single fraction treatment plans with 25 Gy dose prescription based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for ICRU report 91 relevant parameters and crowd dose-volume-histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process.
RESULTS
Twenty centers submitted 67 treatment plans for this study. In most plans (75%) Intensity Modulated Arc Therapy (IMAT) with 6 MV flattening-filter-free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96-100% (19%). Many participants preferred to spare close extra-cardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged 25.5-34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged 2-80 minutes. For the consensus statements, strong agreement was reached for beam technique planning, dose calculation, prescription methods and trade-offs between target and extra-cardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target.
CONCLUSION
This STOPSTORM multi-center treatment planning benchmark study showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established, however clinical data is urgently needed for actionable guidelines for treatment planning
Opportunities and limitations of milk mid-infrared spectra-based estimation of acetone and β-hydroxybutyrate for the prediction of metabolic stress and ketosis in dairy cows.
Subclinical (SCK) and clinical (CK) ketosis are metabolic disorders responsible for big losses in dairy production. Although Fourier-transform mid-infrared spectrometry (FTIR) to predict ketosis in cows exposed to great metabolic stress was studied extensively, little is known about its suitability in predicting hyperketonemia using individual samples, e.g. in small dairy herds or when only few animals are at risk of ketosis. The objective of the present research was to determine the applicability of milk metabolites predicted by FTIR spectrometry in the individual screening for ketosis. In experiment 1, blood and milk samples were taken every two weeks after calving from Holstein (n = 80), Brown Swiss (n = 72) and Swiss Fleckvieh (n = 58) cows. In experiment 2, cows diagnosed with CK (n = 474) and 420 samples with blood β-hydroxybutyrate [BHB] <1.0 mmol/l were used to investigate if CK could be detected by FTIR-predicted BHB and acetone from a preceding milk control. In experiment 3, correlations between data from an in farm automatic milk analyser and FTIR-predicted BHB and acetone from the monthly milk controls were evaluated. Hyperketonemia occurred in majority during the first eight weeks of lactation. Correlations between blood BHB and FTIR-predicted BHB and acetone were low (r = 0.37 and 0.12, respectively, P < 0.0001), as well as the percentage of true positive values (11.9 and 16.6%, respectively). No association of FTIR predicted ketone bodies with the interval of milk sampling relative to CK diagnosis was found. Data obtained from the automatic milk analyser were moderately correlated with the same day FTIR-predicted BHB analysis (r = 0.61). In conclusion, the low correlations with blood BHB and the small number of true positive samples discourage the use of milk mid-infrared spectrometry analyses as the only method to predict hyperketonemia at the individual cow level
The presence and burden of cognitive issues: discordance between the perception of neurologists and people living with multiple sclerosis.
BACKGROUND AND PURPOSE
Cognitive impairment is a common symptom of multiple sclerosis (MS) and occurs in more than 40% of people living with MS (plwMS). No real-world study has assessed the perception of neurologists and plwMS on cognitive issues.
METHODS
Using data from the 2011-2019 Adelphi MS Disease Specific Programme database, this real-world, retrospective, cross-sectional multi-cohort study included people aged ≥18 years with relapsing-remitting MS and secondary progressive MS from the United States, UK and the EU. Neurologists provided data on the patient record form for plwMS, with the same plwMS invited to voluntarily complete a patient self-completion form: a questionnaire about their experiences with MS.
RESULTS
Of 25,374 plwMS, 4817 who provided information on cognitive and mood symptoms were included in the analysis. Of the plwMS, 68% and 59% reported feeling 'mentally fatigued' and having 'difficulty concentrating', respectively. Neurologists reported only 27% of plwMS as having 'difficulty concentrating' and 15% of plwMS as having 'short-/long-term memory problems'. Neurologists reported cognitive or mood symptoms as 'not experienced' by a higher percentage of participants with relapsing-remitting MS than secondary progressive MS. Of the plwMS who experienced 'difficulty concentrating', most had a concomitant feeling of being 'mentally fatigued' (52%), followed by 'feeling anxious or tense' (49%) and 'feeling depressed' (44%). In plwMS, caregivers reported 'difficulty concentrating' (16%) as the most common cognitive issue.
CONCLUSION
A clear discordance was observed between neurologists and plwMS regarding the perception of the cognitive and neuropsychiatric issues. These results underline the under-perception of cognitive and emotional affective symptoms in plwMS during neurological consultations
The role of serotonin in modulating social competence in a cooperatively breeding fish.
Behavioural interactions between conspecifics rely on the appreciation of social cues, which is achieved through biochemical switching of pre-existing neurophysiological pathways. Serotonin is one of the major neurotransmitters in the central nervous system responsible for the modulation of physiological and behavioural traits, in particular social behaviour. The relative importance of serotonin in modulating optimal social responses to the available social information (i.e., social competence) is yet unknown. Here we investigate how serotonin and the serotonin 1A receptor (5-HT1A) modulate social competence in a competitive context. In the cooperatively breeding cichlid Neolamprologus pulcher, we pharmacologically manipulated the serotonin availability and 5-HT1A activity to test their effects on social behaviours during an asymmetric contest between the owner of a defended territory containing a shelter and an intruder devoid of a territory. In this contest, the adequate response by the intruders, the focal individuals in our study, is to show submissive behaviour in order to avoid eviction from the vicinity of the shelter. While the serotonin enhancer Fluoxetine did not affect the frequency of submission towards territory owners, reducing serotonin by a low dosage of 4-Chloro-DL-phenylalanine (PCPA) increased submissive behaviour. Furthermore, threat displays towards territory owners were reduced at high dosages of Fluoxetine and also at the lowest dosage of PCPA. 5-HT1A activation increased threat displays by intruders, indicating that this receptor may not be involved in regulating social competence. We conclude that serotonin, but not its receptor 5-HT1A plays an important role in the regulation of social competence
Fatigue behavior of implant-supported cantilevered prostheses in recently introduced CAD-CAM polymers: An in vitro study.
STATEMENT OF PROBLEM
Cantilevered complete arch implant-supported prostheses are commonly fabricated from zirconia and more recently from strength gradient zirconia. Different polymer-based materials indicated for definitive fixed prostheses that could be used with additive or subtractive manufacturing have also been marketed recently. However, knowledge on the long-term fatigue behavior of cantilevered implant-supported prostheses made from these polymer-based materials and strength gradient zirconia is lacking.
PURPOSE
The purpose of this in vitro study was to evaluate the fatigue behavior of implant-supported cantilevered prostheses of recently introduced computer-aided design and computer-aided manufacturing polymers and zirconia.
MATERIAL AND METHODS
A master standard tessellation language file of a 9×11×20-mm specimen with a titanium base (Ti-base) space that represented an implant-supported cantilevered prosthesis was used to fabricate specimens from additively manufactured interim resin (AM), polymethyl methacrylate (SM-PM), nanographene-reinforced polymethyl methacrylate (SM-GR), high-impact polymer composite resin (SM-CR), and strength gradient zirconia (SM-ZR) (n=10). Each specimen was prepared by following the respective manufacturer's recommendations, and Ti-base abutments were cemented with an autopolymerizing luting composite resin. After cementation, the specimens were mounted in a mastication simulator and subjected to 1.2 million loading cycles under 100 N at 1.5 Hz; surviving specimens were subjected to another 1.2 million loading cycles under 200 N at 1.5 Hz. The load was applied to the cantilever extension, 12-mm from the clamp of the mastication simulator. The Kaplan-Meier survival analysis and Cox proportional hazards model were used to evaluate the data (α=.05).
RESULTS
Significant differences in survival rate and hazard ratio were observed among materials (P<.001). Among tested materials, SM-ZR had the highest and AM had the lowest survival rate (P≤.031). All materials had a significantly higher hazard ratio than SM-ZR (P≤.011) in the increasing order of SM-GR, SM-PM, SM-CR, and AM.
CONCLUSIONS
SM-ZR had the highest survival rate with no failed specimens. Even though most of the tested polymer-based materials failed during cyclic loading, these failures were commonly observed during the second 1.2 million loading cycles with 200 N. All materials had a higher hazard ratio than SM-ZR