8 [3.6] years) were included; 120 children were prescribed once-daily, and 112 twice-daily, ICS. The median PPDC was 66.8% for the once-daily and 57.9% for the twice-daily group (P=.03). Children prescribed once-daily ICS had a 7.2% (95% confidence interval, 1.3-13.1) greater mean PPDC compared with the twice-daily group and greater odds of having PPDC greater than or equal to 75% (71.4% vs 45.5%; odds ratio, 1.80; 95% confidence interval, 1.01-3.26).

Our findings suggest that once-daily dosing of ICS is associated with better medication adherence than twice-daily dosing. Whether the gain in adherence leads to better asthma control and health outcomes remains to be evaluated.

Our findings suggest that once-daily dosing of ICS is associated with better medication adherence than twice-daily dosing. Whether the gain in adherence leads to better asthma control and health outcomes remains to be evaluated.Development of adaptive aids to support human performance in complex systems is a cornerstone of human factors. Research in this area has led to a diversity of ideas regarding potential activation methods. However, little guidance has been provided on how to select among aid activation methods, and this lack of guidance could hinder adaptive aid development and deployment. Within the current paper, we review available methods of aid activation and describe a process for developing and validating adaptive aiding systems. We focus on supporting system designers who wish to select the ideal aid activation method for an intended application. The process that we recommend is an empirical approach to evaluate the feasibility, costs, and benefits of various potential methods of aid activation. This methodological framework will support practitioners making critical decisions about the design of aiding systems.

This study was conducted to compare the healing response of localized gingival recession defects treated with a coronally advanced flap (CAF) and either an amnion allograft membrane (AM) or a connective tissue graft (CTG).

Gingival recession defects were surgically created in six healthy mongrel dogs at the labial root surface of the maxillary canines, bilaterally. Using a split mouth design, the defects were treated with CAF and either AM (CAF/AM) or CTG (CAF/CTG). Three animals for each group were scarified at 1 and 3 months. Segments containing the defects were prepared for histological and histometric analysis.

Both techniques showed similar clinical findings with adequate root coverage. Histologically, healing was characterized by the formation of new cementum and new connective tissue attachment in the CAF/AM group; in the CAF/CTG group, healing was characterized by junctional epithelium, coronally, and connective tissue fibers parallel to the root surface, apically. Histometrically, the CAF/AM group revealed a substantially shorter epithelial length and a longer, new cementum compared with those of the CAF/CTG group after a healing period of 3 months.

Within the limits of this study, we concluded that the AM allograft could promote periodontal healing in gingival recession defects.

Within the limits of this study, we concluded that the AM allograft could promote periodontal healing in gingival recession defects.Among the strategies for bioavailability improvement of poorly soluble drugs, co-amorphous systems have revealed to have a significant impact in the increase of the aqueous solubility of the drug, and at the same time increasing the amorphous state stability and dissolution rate when compared with the neat drug. Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes. TBM is a class II drug according to the Biopharmaceutical Classification System, meaning that it has low solubility and higher permeability. The aim of this study was to synthesize a co-amorphous material of tolbutamide (TBM) with tromethamine (TRIS). Density functional theory (DFT), allowed to study the structural, electronic, and thermodynamic properties, as well as solvation effects. In same theory level, several interactions tests were performed to obtain the most thermodynamically favorable drug-coformer intermolecular interactions. The vibrational spectra (mid infrared and Raman spectroscopy) are in accordance with the theoretical studies, showing that the main molecular interactions are due to the carbonyl, sulfonyl, and amide groups of TMB and the alcohol and amine groups of TRIS. X-ray powder diffraction was used to study the physical stability in dry condition at 25 °C of the co-amorphous system, indicating that the material remained in an amorphous state up to 90 days. Differential scanning calorimetry and thermogravimetric results showed a high increase of the Tg when compared with the amorphous neat drug, from 4.3 °C to 83.7 °C, which generally translated into good physical stability. Solubility studies demonstrated an increase in the solubility of TBM by 2.5 fold when compared with its crystalline counterpart.Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that a lectibody consisting of the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon, and blood cancers at nanomolar concentrations. Binding of AvFc to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody’s common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly restricted A549 and H460 tumor growth in severe combined immunodeficiency (SCID) mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.Acute pancreatitis (AP) is a common digestive disease without specific treatment, and its pathogenesis features multiple deleterious amplification loops dependent on translation, triggered by cytosolic Ca2+ ([Ca2+]i) overload; however, the underlying mechanisms in Ca2+ overload of AP remains incompletely understood. Here we show that microRNA-26a (miR-26a) inhibits pancreatic acinar cell (PAC) store-operated Ca2+ entry (SOCE) channel expression, Ca2+ overload, and AP. We find that major SOCE channels are post-transcriptionally induced in PACs during AP, whereas miR-26a expression is reduced in experimental and human AP and correlated with AP severity. Mechanistically, miR-26a simultaneously targets Trpc3 and Trpc6 SOCE channels and attenuates physiological oscillations and pathological elevations of [Ca2+]i in PACs. MiR-26a deficiency increases SOCE channel expression and [Ca2+]i overload, and significantly exacerbates AP. Conversely, global or PAC-specific overexpression of miR-26a in mice ameliorates pancreatic edema, neutrophil infiltration, acinar necrosis, and systemic inflammation, accompanied with remarkable improvements on pathological determinants related with [Ca2+]i overload. Moreover, pancreatic or systemic administration of an miR-26a mimic to mice significantly alleviates experimental AP. These findings reveal a previously unknown mechanism underlying AP pathogenesis, establish a critical role for miR-26a in Ca2+ signaling in the exocrine pancreas, and identify a potential target for the treatment of AP.Exercise and its regulated molecules have myocardial protective effects against cardiac ischemia/reperfusion (I/R) injury. The muscle-enriched miR-486 was previously identified to be upregulated in the exercised heart, which prompted us to investigate the functional roles of miR-486 in cardiac I/R injury and to further explore its potential in contributing to exercise-induced protection against I/R injury. Our data showed that miR-486 was significantly downregulated in the heart upon cardiac I/R injury. Both preventive and therapeutic interventions of adeno-associated virus 9 (AAV9)-mediated miR-486 overexpression could reduce cardiac I/R injury. Using AAV9 expressing miR-486 with a cTnT promoter, we further demonstrated that cardiac muscle cell-targeted miR-486 overexpression was also sufficient to protect against cardiac I/R injury. Consistently, miR-486 was downregulated in oxygen-glucose deprivation/reperfusion (OGDR)-stressed cardiomyocytes, while upregulating miR-486 inhibited cardiomyocyte apoptosis through PTEN and FoxO1 inhibition and AKT/mTOR activation. Finally, we observed that miR-486 was necessary for exercise-induced protection against cardiac I/R injury. In conclusion, miR-486 is protective against cardiac I/R injury and myocardial apoptosis through targeting of PTEN and FoxO1 and activation of the AKT/mTOR pathway, and mediates the beneficial effect of exercise for myocardial protection. Increasing miR-486 might be a promising therapeutic strategy for myocardial protection.

The Australasian Resuscitation Outcomes Consortium (Aus-ROC) out-of-hospital cardiac arrest (OHCA) Epistry (Epidemiological Registry) now covers 100% of Australia and New Zealand (NZ). This study reports and compares the Utstein demographics, arrest characteristics and outcomes of OHCA patients across our region.

We included all OHCA cases throughout 2019 as submitted to the Epistry by the eight Australian and two NZ emergency medical services (EMS). We calculated crude and age-standardised incidence rates and performed a national and EMS regional comparison.

We obtained data for 31,778 OHCA cases for 2019 26,637 in Australia and 5,141 in NZ. Crude incidence was 107.9 per 100,000 person-years in Australia and 103.2/100,000 in NZ. Overall, the majority of OHCAs occurred in adults (96%), males (66%), private residences (76%), were unwitnessed (63%), of presumed medical aetiology (83%), and had an initial monitored rhythm of asystole (64%). In non-EMS-witnessed cases, 38% received bystander CPR and 2% received public defibrillation. Wide variation was seen between EMS regions for all OHCA demographics, arrest characteristics and outcomes. In patients who received an EMS-attempted resuscitation (13,664/31,778) 28% (range across EMS=13.1% to 36.7%) had return of spontaneous circulation (ROSC) at hospital arrival and 13% (range across EMS=9.9% to 20.7%) survived to hospital discharge/30-days. Survival in the Utstein comparator group (bystander-witnessed in shockable rhythm) varied across the EMS regions between 27.4% to 42.0%.

OHCA across Australia and NZ has varied incidence, characteristics and survival. Understanding the variation in survival and modifiable predictors is key to informing strategies to improve outcomes.

OHCA across Australia and NZ has varied incidence, characteristics and survival. Understanding the variation in survival and modifiable predictors is key to informing strategies to improve outcomes.