Auxetic piezoelectric effect in heterostructures.

Inherent symmetry breaking at the interface has been fundamental to a myriad of physical effects and functionalities, such as efficient spin-charge interconversion, exotic magnetic structures and an emergent bulk photovoltaic effect. It has recently been demonstrated that interface asymmetry can induce sizable piezoelectric effects in heterostructures, even those consisting of centrosymmetric semiconductors, which provides flexibility to develop and optimize electromechanical coupling phenomena. Here, by targeted engineering of the interface symmetry, we achieve piezoelectric phenomena behaving as the electrical analogue of the negative Poisson's ratio. This effect, termed the auxetic piezoelectric effect, exhibits the same sign for the longitudinal (d33) and transverse (d31, d32) piezoelectric coefficients, enabling a simultaneous contraction or expansion in all directions under an external electrical stimulus. The signs of the transverse coefficients can be further tuned via in-plane symmetry anisotropy. The effects exist in a wide range of material systems and exhibit substantial coefficients, indicating potential implications for all-semiconductor actuator, sensor and filter applications.

Charge-Based Separation of Microparticles Using AC Insulator-Based Dielectrophoresis.

Surface charge is an important property of particles. It has been utilized to separate particles in microfluidic devices, where dielectrophoresis (DEP) is often the driving force. However, current DEP-based particle separations based on the charge differences work only for particles of similar sizes. They become less effective and may even fail for a mixture of particles differing in both charge and size. We demonstrate that our recently developed AC insulator-based dielectrophoresis (AC iDEP) technique can direct microparticles toward charge-dependent equilibrium positions in a ratchet microchannel. Such charge-based particle separation is controlled by the imposed AC voltage frequency and amplitude but is nearly unaffected by the size of either type of particle in the mixture except for the time required to achieve an effective separation. This AC iDEP technique may potentially be used to focus and separate submicron or even nanoparticles because of its virtually "infinite" channel length.

Divergent effects of emm types 1 and 12 on invasive group A streptococcal infections-results of a retrospective cohort study, Germany 2023.

As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (emm types) and superantigens in patients with invasive and non-invasive GAS infections. From December 2022 to December 2023, a total of 163 GAS isolates were collected from sterile and non-sterile sites of patients at five hospitals in Germany including two tertiary care centers. Genes encoding M protein and superantigens were determined following the guidelines of CDC Streptococcus laboratory. Patients' characteristics were reviewed retrospectively. Correlations of clinical factors, emm types, and superantigens with rates of invasive infections were analyzed. Of the 163 included GAS cases, 112 (69%) were considered as invasive. In total, 33 different emm types were observed, of which emm1.0 (n = 49; 30%), emm89.0 (n = 15; 9%), and emm12.0 (n = 14; 9%) were most prevalent. In total, 70% of emm1.0 isolates belonged to M1UK lineage. No difference in invasive infections was observed for the M1UK lineage compared with other emm1.0 isolates. However, the emm1.0 type, presence of speA1-3, speG, or speJ, as well as adulthood were significantly associated with invasive infections. In contrast, emm12.0 isolates were significantly less associated with invasive infections. Multivariable analysis confirmed a significant influence of speJ and adulthood on iGAS infections. This study underlines the importance of continuous monitoring of genomic trends and identification of emerging GAS variants. This may aid in delineating pathogenicity factors of Streptococcus pyogenes that propel invasive infections.

Rotary excitation of non-sinusoidal pulsed magnetic fields: Towards non-invasive direct detection of cardiac conduction.

PURPOSE: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range. METHODS: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields. The REX detection approach was validated under controlled conditions in phantom experiments at 3 T. Gaussian and sinc-shaped stimuli were investigated. In addition, the detection of artificial fields resembling a cardiac QRS complex, which is the most prominent peak visible on a magnetocardiogram, was tested. RESULTS: Bloch simulations demonstrated that the REX method has a high sensitivity to pulsed fields in the resonance case, which is met when the spin-lock frequency coincides with a non-zero Fourier component of the stimulus field. In the experiments, we found that magnetic stimuli of different durations and waveforms can be distinguished by their characteristic REX response spectrum. The detected REX amplitude was proportional to the stimulus peak amplitude (R2 > 0.98) and the lowest field detection was 1 nT. Furthermore, the detection of QRS-like fields with varying QRS durations yielded significant results in a phantom setup (p < 0.001). CONCLUSION: REX detection can be transferred to non-sinusoidal pulsed magnetic fields and could provide a non-invasive, quantitative tool for spatially resolved assessment of cardiac biomagnetism. Potential applications include the direct detection and characterization of cardiac conduction.

Quantification of the rotating frame relaxation time T2ρ: Comparison of balanced spin-lock and continuous-wave Malcolm-Levitt preparations.

For the quantification of rotating frame relaxation times, the T2ρ relaxation pathway plays an essential role. Nevertheless, T2ρ imaging has been studied only to a small extent compared with T1ρ, and preparation techniques for T2ρ have so far been adapted from T1ρ methods. In this work, two different preparation concepts are compared specifically for the use of T2ρ mapping. The first approach involves transferring the balanced spin-locking (B-SL) concept of T1ρ imaging. The second and newly proposed approach is a continuous-wave Malcolm-Levitt (CW-MLEV) pulse train with zero echo times and was motivated from T2 preparation strategies. The modules are tested in Bloch simulations for their intrinsic sensitivity to field inhomogeneities and validated in phantom experiments. In addition, myocardial T2ρ mapping was performed in mice as an exemplary application. Our results demonstrate that the CW-MLEV approach provides superior robustness and thus suggest that established methods of T1ρ imaging are not best suited for T2ρ experiments. In the presence of field inhomogeneities, the simulations indicated an increased banding compensation by a factor of 4.1 compared with B-SL. Quantification of left ventricular T2ρ time in mice yielded more consistent results, and values in the range of 59.2-61.1 ms (R2 = 0.986-0.992) were observed at 7 T.

Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

Elective direct current cardioversion of atrial fibrillation - silent brain infarction and health related quality of life.

INTRODUCTION: Atrial fibrillation (AF) increases the risk for stroke, dementia and impaired health related quality of life (HRQL). Elective direct current cardioversion (ECV) is often used to restore sinus rhythm, but is associated with thromboembolism. While larger strokes usually produce symptoms, subclinical ones may go unrecognized and may cause cognitive and functional decline over time. In the current study, we sought to evaluate the effects of ECV on silent brain infarctions and HRQL in patients with AF. METHODS: Patients with AF (n=46) underwent brain magnetic resonance imaging (MRI) and HRQL assessment using the EuroQL-5D5L questionnaire before and after ECV. Implantable loop recorders (ILR) were used to observe the rate of early AF recurrences within the first thirty days. All patients were treated with anticoagulants according to guidelines. The primary endpoint was silent brain infarction assessed by brain MRI within the first two weeks after ECV. Secondary endpoints were the change in HRQL and its association with AF recurrence at follow-up and by ILR recordings. RESULTS: New silent brain infarction after ECV was detected in one patient. At follow-up visit after 19.1 days AF recurrence was detected by 12-lead ECG in 13 patients (28.3 %), whereas 27 patients (58.7 %) had AF recurrence recorded by ILR within the first thirty days after ECV. European Heart Rhythm Association (EHRA) symptom score and the EuroQL-5d5L score were improved after ECV. CONCLUSION: Silent brain infarctions may occur after ECV despite anticoagulation treatment. Early AF recurrence is frequent. ECV positively affects HRQL mainly in those patients with sustained sinus rhythm at follow-up.

Establishment of a Novel Short Tandem Repeat Typing Method for Exophiala dermatitidis.

The opportunistic black yeast-like fungus Exophiala dermatitidis frequently colonizes the respiratory tract of cystic fibroses (CF) patients. Additionally, it can cause superficial, systemic, and cerebral forms of phaeohyphomycoses. The objective of this study was to develop and apply a microsatellite or short tandem repeat (STR) genotyping scheme for E. dermatitidis. In total, 82 E. dermatitidis isolates from various geographic origins (environmental = 9, CF = 63, invasive isolates = 9, melanin-deficient mutant = 1) were included in this study. After next-generation sequencing of a reference strain and sequence filtering for microsatellites, six STR markers were selected and amplified in two multiplex PCR reactions. The included isolates were discriminated in a genetic cluster analysis using the Pearson algorithm to reveal the relatedness of the isolates. The E. dermatitidis isolates clustered on basis of both, their source and their origin. The invasive isolates from Asia were unrelated to isolates from CF. Nearly all environmental isolates were grouped separately from patients' isolates. The Simpson index was 0.94. In conclusion, we were able to establish a STR genotyping scheme for investigating population genomics of E. dermatitidis.

H2BFWT Variations in Sperm DNA and Its Correlation to Pregnancy.

Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed to study the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509, and rs578953. Significant differences were shown in the distribution of alternative and reference alleles between G1 and G2 (p = 0.0004 and p = 0.0020, respectively) for rs553509 and rs578953. However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels will help to determine its functional consequences and to clarify the mechanism of how pregnancy can be affected by sperm DNA.

Deliberate Compensated Vasoplegia-A Novel Pharmaceutical Approach for Controlling Blood Pressure During Surgery for Pheochromocytoma.

BACKGROUND: The most dreaded adverse event of pheochromocytoma surgery is operative severe blood pressure fluctuations. Preoperative protocols with alpha-blockade have achieved controversial results. No study to date evaluated the use of operative protocols in pheochromocytoma patients. Deliberated compensated vasoplegia (DCV) is a novel pharmaceutical regimen developed at our institution to decrease severe hypertensive events. The aim of this study is to compare outcomes of pheochromocytoma resection with and without DCV protocol. METHODS: A retrospective analysis of all pheochromocytoma resections between the years 2012 and 2021 was performed. Resections performed with and without DCV protocol were compared. The primary outcome measured was the incidence of severe hypertension (MAP > 150 mmHg) during surgery. Secondary outcomes included other abnormal blood pressure measurements as well as perioperative data and complications. RESULTS: A total of 41 resections were included, 21 performed under DCV protocol, and 20 without the protocol. Analysis demonstrated no significant difference in preoperative parameters including tumor size, catecholamine levels, and preoperative alpha-blockade protocol. The use of DCV protocol resulted in significant decrease in severe hypertension incidence from 1.95 ± 3.6 to 0.03 ± 0.13 events/h, p = 0.008. Application of the DCV protocol was not associated with any other adverse events. CONCLUSIONS: This study suggests that DCV anesthesia protocol significantly decreases the incidence of severe hypertensive episodes during pheochromocytoma resection. This is the first study that describes a highly effective protocol for controlling hypertension in pheochromocytoma patients.

Depression and associated factors among Brazilian adults: the 2019 national healthcare population-based study.

BACKGROUND: Mental disorders represent a major public health challenge worldwide, affecting 80% of people living in low- and middle-income countries. Depression, a mental disorder, is a chronic disease of long duration that causes changes in the brain, resulting from a combination of genetic, physiologic, environmental, and behavioral factors. The aim of this study was to investigate possible factors associated with depression in Brazilian adults. METHODS: A population-based, cross-sectional study was carried out using the public domain database of the 2019 National Health Survey, conducted in Brazil. Depression was considered the dependent variable, and through hierarchical analysis, predictor variables were investigated such as, at the distal level-socioeconomic variables, at the intermediate level-variables related to lifestyle behavior, health condition, and history, and at the proximal level-demographic variables. Logistic regression analysis was used to obtain the adjusted Odds Ratio and the respective 95% confidence interval to identify possible factors associated with depression. RESULTS: The study included 88,531 participant records with 10.27% diagnosed with depression. The adjusted association measurements, after selecting the independent variables in the hierarchical analysis, showed the following factors associated with depression with differing magnitudes: age, brown and white race/skin color, female sex, poor, very poor, or regular self-reported health condition, diagnosis of cardiovascular disease, work-related musculoskeletal disorder, history of smoking habit, and macroeconomic region. CONCLUSIONS: An effective strategy for preventing and managing depression in Brazilian adults must include the control of health status and lifestyle behavior factors, with actions and programs to reduce people's exposure to these factors, understanding that socioeconomic-demographic differences of each population can potentially reduce the disease burden.

DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber's hereditary optic neuropathy and optic atrophy.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) has been considered a prototypical mitochondriopathy and a textbook example for maternal inheritance linked to certain disease-causing variants in the mitochondrial genome. Recently, an autosomal recessive form of LHON (arLHON) has been described, caused by disease-causing variants in the nuclear encoded gene DNAJC30. METHODS AND RESULTS: In this study, we screened the DNAJC30 gene in a large Central European cohort of patients with a clinical diagnosis of LHON or other autosomal inherited optic atrophies (OA). We identified likely pathogenic variants in 35/1202 patients, corresponding to a detection rate of 2.9%. The previously described missense variant c.152A>G;p.(Tyr51Cys) accounts for 90% of disease-associated alleles in our cohort and we confirmed a strong founder effect. Furthermore, we identified two novel pathogenic variants in DNAJC30: the nonsense variant c.610G>T;p.(Glu204*) and the in-frame deletion c.230_232del;p.(His77del). Clinical investigation of the patients with arLHON revealed a younger age of onset, a more frequent bilateral onset and an increased clinically relevant recovery compared with LHON associated with disease-causing variants in the mitochondrial DNA. CONCLUSION: This study expands previous findings on arLHON and emphasises the importance of DNAJC30 in the genetic diagnostics of LHON and OA in European patients.

Periodontitis severity relationship with metabolic syndrome: A systematic review with meta-analysis.

The objective of this study was to investigate the association between periodontitis severity and metabolic syndrome (MetS) through systematic review, registered in PROSPERO: CRD42021232120. Selected articles were independently chosen by three reviewers from six databases, including using article reference lists, up until March 2022. Eligible studies were observational, without language limitation, and in subjects aged at least 18 years. The methodological quality of selected studies was assessed using the Newcastle-Ottawa Scale. Random effects models calculated summary measurements (odds ratio-OR, 95% confidence interval, 95%CI). The I2 test evaluated the statistical heterogeneity of the data. Sensitivity, subgroup, and meta-regression analyses were performed. For the reliability of evidence, the Grading of Recommendations, Assessment, Development, and Evaluations tool was used. A total of 2133 records were identified, and 14 studies were included comprising 24,567 participants. The summary odds ratio showed a positive association between individuals with moderate (ORadjusted  = 1.26; 95%CI = 2.10-5.37; I2  = 45.85%), and severe periodontitis (ORadjusted  = 1.50; 95%CI:1.28-1.71; I2  = 56.46%), and MetS. Subgroup and meta-regression analyses showed that study effect size was influenced by year of publication, study design, and MetS diagnostic criteria, contributing to inter-study variability. The findings showed that moderate and severe levels of periodontitis are associated with MetS, suggesting a possible dose-response effect.

Carbon dioxide protects simulated driving performance during severe hypoxia.

PURPOSE: We sought to determine the effect of acute severe hypoxia, with and without concurrent manipulation of carbon dioxide (CO2), on complex real-world psychomotor task performance. METHODS: Twenty-one participants completed a 10-min simulated driving task while breathing room air (normoxia) or hypoxic air (PETO2 = 45 mmHg) under poikilocapnic, isocapnic, and hypercapnic conditions (PETCO2 = not manipulated, clamped at baseline, and clamped at baseline + 10 mmHg, respectively). Driving performance was assessed using a fixed-base motor vehicle simulator. Oxygenation in the frontal cortex was measured using functional near-infrared spectroscopy. RESULTS: Speed limit exceedances were greater during the poikilocapnic than normoxic, hypercapnic, and isocapnic conditions (mean exceedances: 8, 4, 5, and 7, respectively; all p ≤ 0.05 vs poikilocapnic hypoxia). Vehicle speed was greater in the poikilocapnic than normoxic and hypercapnic conditions (mean difference: 0.35 km h-1 and 0.67 km h-1, respectively). All hypoxic conditions similarly decreased cerebral oxyhaemoglobin and increased deoxyhaemoglobin, compared to normoxic baseline, while total hemoglobin remained unchanged. CONCLUSIONS: These findings demonstrate that supplemental CO2 can confer a neuroprotective effect by offsetting impairments in complex psychomotor task performance evoked by severe poikilocapnic hypoxia; however, differences in performance are unlikely to be linked to measurable differences in cerebral oxygenation.

Targeting the Granulocytic Defense against A. fumigatus in Healthy Volunteers and Septic Patients.

Neutrophil granulocytes (NGs) are among the key players in the defense against Aspergillus fumigatus (A. fumigatus). To better elucidate a pathophysiological understanding of their role and functions, we applied a human cell model using NGs from healthy participants and septic patients to evaluate their inhibitory effects on the growth of A. fumigatus ex vivo. Conidia of A. fumigatus (ATCC® 204305) were co-incubated with NGs from healthy volunteers or septic patients for 16 h. A. fumigatus growth was measured by XTT assays with a plate reader. The inhibitory effect of NGs on 18 healthy volunteers revealed great heterogeneity. Additionally, growth inhibition was significantly stronger in the afternoon than the morning, due to potentially different cortisol levels. It is particularly interesting that the inhibitory effect of NGs was reduced in patients with sepsis compared to healthy controls. In addition, the magnitude of the NG-driven defense against A. fumigatus was highly variable among healthy volunteers. Moreover, daytime and corresponding cortisol levels also seem to have a strong influence. Most interestingly, preliminary experiments with NGs from septic patients point to a strongly diminished granulocytic defense against Aspergillus spp.

Sortase A Inhibitor Protein Nanoparticle Formulations Demonstrate Antibacterial Synergy When Combined with Antimicrobial Peptides.

Sortase A (SrtA) is an enzyme which attaches proteins, including virulence factors, to bacterial cell walls. It is a potential target for developing anti-virulence agents against pathogenic and antimicrobial resistant bacteria. This study aimed to engineer 𝛽-lactoglobulin protein nanoparticles (PNPs) for encapsulating safe and inexpensive natural SrtA inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), and berberine (BR)) to improve their poor aqueous dispersibility, to screen for synergy with antimicrobial peptides (AMPs), and to reduce the cost, dose, and toxicity of AMPs. Minimum inhibitory concentration (MIC), checkerboard synergy, and cell viability assays were performed for SrtAI PNPs against Gram-positive (methicillin-sensitive and -resistant S. aureus) and Gram-negative (E. coli, P. aeruginosa) bacteria alone and combined with leading AMPs (pexiganan, indolicidin, and a mastoparan derivative). Each SrtAI PNP inhibited Gram-positive (MIC: 62.5-125 µg/mL) and Gram-negative (MIC: 31.3-500 µg/mL) bacterial growth. TC PNPs with pexiganan demonstrated synergy against each bacteria, while BR PNPs with pexiganan or indolicidin provided synergy towards S. aureus. Each SrtAI PNP inhibited SrtA (IC50: 25.0-81.8 µg/mL), and did not affect HEK-293 cell viability at their MIC or optimal synergistic concentrations with AMPs. Overall, this study provides a safe nanoplatform for enhancing antimicrobial synergy to develop treatments for superbug infections.

COVID-19 perceived stigma among survivors: A cross-sectional study of prevalence and predictors.

Background and objectives: Perceived stigma related to infectious diseases is of public health importance and can adversely impact patients' physical and mental health. This study aims to identify the level of perceived stigma among COVID-19 survivors in Qatar and investigate its predictors. Methods: An analytical cross-sectional design was employed. Four hundred and four participants who had a positive COVID-19 PCR test were randomly selected from medical records. The selected participants were interviewed to collect sociodemographic and health-related information. Perceived stigma was assessed using the COVID-19 perceived stigma scale-22 (CPSS-22) that was developed by the researchers. A descriptive analysis followed by a bivariate analysis investigated possible associations between the perceived stigma levels and independent variables. A multivariable analysis was performed using logistic regression to identify any significant associations with perceived stigma. The validity and reliability of the developed tool were also tested. Results: The prevalence of COVID-19 perceived stigma was twenty-six percent (n = 107, 26.4%) at 95% CI [22.4-30.4]. Factors associated with higher COVID-19 perceived stigma were male gender, being a manual worker, non-Arabic ethnicity, low educational level, living alone, and being isolated outside the home. However, only occupation, ethnicity, and low educational level predicted COVID-19 perceived stigma in multivariable analysis. The CPSS-22 showed excellent reliability (Cronbach's alpha 0.92). Conclusion: Perceived stigma was relatively common among participants. Designing programs and interventions targeting male manual workers and those of low-educational levels may assist policymakers in mitigating the stigma related to COVID-19.

Improving oral health of adolescent girls in Kenya through education - An observational study.

OBJECTIVES: Dental caries and periodontal diseases are significant health concerns in developing nations. This study assessed the impact of a comprehensive oral health education program on adolescent girls in rural Kenya. METHODS: Eighty-seven girls aged 13-18 years attending school in rural Nanyuki, Kenya, were enrolled in the study. The comprehensive program included personalized oral hygiene training, education and health advocacy coaching. Dental caries, gingival inflammation and dental plaque biofilm were assessed at baseline, 1- and 2.5-year post-implementation. RESULTS: The intervention was highly effective in arresting pre-existing carious lesions and preventing the formation of new ones in this population. The data revealed that there was a significant remineralization of incipient caries lesion, as shown by decreases in modified ICCMS™ scores from baseline to 1-year post-implementation. From baseline to the 2.5-year post-implementation assessment, only six new carious lesions developed. Dental plaque biofilm was reduced by 83.6%, and gingival inflammation was reduced by 81.6%. CONCLUSION: A comprehensive oral health program, which included behavioural awareness and educational approaches, resulted in significant positive oral health outcomes in caries, dental plaque biofilm and gingival inflammation.

Inhibition of azole-resistant Aspergillus fumigatus biofilm at various formation stages by antifungal drugs, including olorofim.

OBJECTIVES: Interest in aspergillosis has increased over the past decades. An increase in the incidence of azole-resistant Aspergillus fumigatus strains has been reported; therefore, the need for novel therapeutic approaches is urgent. The formation of biofilms contributes to pathogen resistance. We investigated the biofilm formation capabilities of azole-resistant A. fumigatus and analysed the susceptibility of biofilms at various developmental stages to three antifungal agents. METHODS: Biofilm formation of 19 clinical A. fumigatus strains (3 azole-susceptible and 16 azole-resistant strains) was determined by crystal violet staining and by an XTT assay over a period of 48 h. We measured antibiofilm activity of voriconazole, amphotericin B and olorofim. These agents were added before adhesion, after adhesion, after germination and to mature fungal biofilm. Antibiofilm activity was assessed in an XTT assay and in confocal laser scan microscopy. Additionally, a growth-kinetic assay with planktonic A. fumigatus was performed. RESULTS: Each of the antifungal agents inhibited the metabolic activity of A. fumigatus biofilms when applied at early stages of biofilm formation. The mature biofilms were more resistant. Olorofim and voriconazole showed promising effects against A. fumigatus adhesion and germination, whereas the mature biofilm was not affected by treatment. In contrast, the biofilm of A. fumigatus showed amphotericin B susceptibility throughout the entire developmental process. The planktonic cells were susceptible to all three antifungal drug classes with an inhibition peak at 12 h after incubation. CONCLUSIONS: This is the first known study to demonstrate the antibiofilm activity of olorofim, voriconazole and amphotericin B against azole-resistant A. fumigatus.

Quantification correction for free-breathing myocardial T1ρ mapping in mice using a recursively derived description of a T1ρ* relaxation pathway.

BACKGROUND: Fast and accurate T1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T1ρ relaxation pathway. In this study, we present an improved quantification method for T1ρ using a newly derived formalism of a T1ρ* relaxation pathway. METHODS: The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T1ρ mapping in mice. Here, the impact of the breath dependent spin recovery time Trec on the quantification results was examined in detail. RESULTS: Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from - 7.4% to - 0.97%. In vivo, a correlation of uncorrected T1ρ with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T1ρ values in different animals was reduced by at least 39%. CONCLUSION: The suggested quantification formalism enables fast and precise myocardial T1ρ quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results.