An analysis of adaptations to multi-level intervention strategies to enhance implementation of clinical practice guidelines for treating tobacco use in dental care settings

Introduction Our team conducted a cluster randomized controlled trial (DUET) that compared the effectiveness of three theory-driven, implementation strategies on dental provider adherence to tobacco dependence treatment guidelines (TDT). In this paper we describe the process of adapting the implementation strategies to the local context of participating dental public health clinics in New York City. Methods Eighteen dental clinics were randomized to one of three study arms testing several implementation strategies: Current Best Practices (CBP) (i.e. staff training, clinical reminder system and Quitline referral system); CBP + Performance Feedback (PF) (i.e. feedback reports on provider delivery of TDT); and CBP + PF + Pay-for-Performance (i.e. financial incentives for provision of TDT). Through an iterative process, we used Stirman's modification framework to classify, code and analyze modifications made to the implementation strategies. Results We identified examples of six of Stirman's twelve content modification categories and two of the four context modification categories. Content modifications were classified as: tailoring, tweaking or refining (49.8%), adding elements (14.1%), departing from the intervention (9.3%), loosening structure (4.4%), lengthening and extending (4.4%) and substituting elements (4.4%). Context modifications were classified as those related to personnel (7.9%) and to the format/channel (8.8%) of the intervention delivery. Common factors associated with adaptations that arose during the intervention included staff changes, time constraints, changes in leadership preferences and functional limitations of to the Electronic Dental Record. Conclusions This study offers guidance on how to capture intervention adaptation in the context of a multi-level intervention aimed at implementing sustainable changes to optimize TDT in varying public health dental settings

ZnO-based scintillating bolometers: New prospects to study double beta decay of 64^{64}Zn

The first detailed study on the performance of a ZnO-based cryogenic scintillating bolometer as a detector to search for rare processes in zinc isotopes was performed. A 7.2 g ZnO low-temperature detector, containing more than 80\% of zinc in its mass, exhibits good energy resolution of baseline noise 1.0--2.7 keV FWHM at various working temperatures resulting in a low-energy threshold for the experiment, 2.0--6.0 keV. The light yield for $\beta$/$\gamma$ events was measured as 1.5(3) keV/MeV, while it varies for $\alpha$ particles in the range of 0.2--3.0 keV/MeV. The detector demonstrate an effective identification of the $\beta$/$\gamma$ events from $\alpha$ events using time-properties of only heat signals. %(namely, Rise time parameter). The radiopurity of the ZnO crystal was evaluated using the Inductively Coupled Plasma Mass Spectrometry, an ultra-low-background High Purity Ge $\gamma$-spectrometer, and bolometric measurements. Only limits were set at the level of $\mathcal{O}$(1--100) mBq/kg on activities of \Nuc{K}{40}, \Nuc{Cs}{137} and daughter nuclides from the U/Th natural decay chains. The total internal $\alpha$-activity was calculated to be 22(2) mBq/kg, with a major contribution caused by 6(1) mBq/kg of \Nuc{Th}{232} and 12(2) mBq/kg of \Nuc{U}{234}. Limits on double beta decay (DBD) processes in \Nuc{Zn}{64} and \Nuc{Zn}{70} isotopes were set on the level of $\mathcal{O}(10^{17}$--$10^{18})$ yr for various decay modes profiting from 271 h of acquired background data in the above-ground lab. This study shows a good potential for ZnO-based scintillating bolometers to search for DBD processes of Zn isotopes, especially in \Nuc{Zn}{64}, with the most prominent spectral features at $\sim$10--20 keV, like the two neutrino double electron capture. A 10 kg-scale experiment can reach the experimental sensitivity at the level of $\mathcal{O}(10^{24})$ yr.Comment: Prepared for submission to JINST; 27 pages, 9 figures, and 7 table

Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system

The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice

Role of oesophageal cooling in the prevention of oesophageal injury in atrial fibrillation catheter ablation: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To evaluate the efficacy of oesophageal cooling in the prevention of oesophageal injury in patients undergoing atrial fibrillation (AF) catheter ablation. METHODS AND RESULTS: Comprehensive search of MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) evaluating the role of oesophageal cooling compared with control in the prevention of oesophageal injury during AF catheter ablation. The study primary outcome was the incidence of any oesophageal injury. The meta-analysis included 4 RCTs with a total of 294 patients. There was no difference in the incidence of any oesophageal injury between oesophageal cooling and control [15% vs. 19%; relative risk (RR) 0.86; 95% confidence interval (CI) 0.31-2.41]. Compared with control, oesophageal cooling showed lower risk of severe oesophageal injury (1.5% vs. 9%; RR 0.21; 95% CI 0.05-0.80). There were no significant differences among the two groups in mild to moderate oesophageal injury (13.6% vs. 12.1%; RR 1.09; 95% CI 0.28-4.23), procedure duration [standardized mean difference (SMD) -0.03; 95% CI -0.36-0.30], posterior wall radiofrequency (RF) time (SMD 0.27; 95% CI -0.04-0.58), total RF time (SMD -0.50; 95% CI -1.15-0.16), acute reconnection incidence (RR 0.93; 95% CI 0.02-36.34), and ablation index (SMD 0.16; 95% CI -0.33-0.66). CONCLUSION: Among patients undergoing AF catheter ablation, oesophageal cooling did not reduce the overall risk of any oesophageal injury compared with control. Oesophageal cooling might shift the severity of oesophageal injuries to less severe injuries. Further studies should evaluate the long-term effects after oesophageal cooling during AF catheter ablation

Y-Chromosomal Diversity in Lebanon Is Structured by Recent Historical Events

Lebanon is an eastern Mediterranean country inhabited by approximately four million people with a wide variety of ethnicities and religions, including Muslim, Christian, and Druze. In the present study, 926 Lebanese men were typed with Y-chromosomal SNP and STR markers, and unusually, male genetic variation within Lebanon was found to be more strongly structured by religious affiliation than by geography. We therefore tested the hypothesis that migrations within historical times could have contributed to this situation. Y-haplogroup J∗(xJ2) was more frequent in the putative Muslim source region (the Arabian Peninsula) than in Lebanon, and it was also more frequent in Lebanese Muslims than in Lebanese non-Muslims. Conversely, haplogroup R1b was more frequent in the putative Christian source region (western Europe) than in Lebanon and was also more frequent in Lebanese Christians than in Lebanese non-Christians. The most common R1b STR-haplotype in Lebanese Christians was otherwise highly specific for western Europe and was unlikely to have reached its current frequency in Lebanese Christians without admixture. We therefore suggest that the Islamic expansion from the Arabian Peninsula beginning in the seventh century CE introduced lineages typical of this area into those who subsequently became Lebanese Muslims, whereas the Crusader activity in the 11th–13th centuries CE introduced western European lineages into Lebanese Christians

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities