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Genetic ablation associated with Tacr2 unveils the overlap golf as well as redundant functions involving NK2R signaling in the control of reproductive : axis.
The clinic prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT 4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT 4 A showed about 60-fold higher sonodynamic ROS generation in aggregation form than disaggregation form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The levels of AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle sizes of their aggregates. Moreover, biological studies demonstrated that ZnPcT 4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
In spite of adolescents' rights to be involved in decisions that concern their health and life, limited research has been published reporting on their involvement in mental health research. Therefore, we aim to present experiences and reflections based on the involvement of adolescents in mental health research, to describe the collaborative relationship between researchers and coresearchers, including the values that underpin their collaboration.

An autoethnographic approach was used, combined with group reflections. The process was jointly developed, carried out and analysed by adolescent coresearchers and the project's lead researcher over a period of 2 years. The article is jointly authored by the researcher and the ten coresearchers.

Six themes were developed to describe our collaborative relationship, resulting in the involvement of adolescents in decisions about research priorities; in planning and carrying out the research; through to analysis, dissemination and communication of results. The the project and as coauthors of this article, including planning, participation in the self- and group-reflective processes, analysis and authoring the article.
Adolescents have contributed as coresearchers through all phases of the research project and as coauthors of this article, including planning, participation in the self- and group-reflective processes, analysis and authoring the article.
Von Willebrand disease (VWD) is the most common inherited bleeding disorder. The bleeding phenotype is variable, and some individuals have persistent symptoms post-diagnosis.

To characterize bleeding patterns in patients with VWD before and after diagnosis.

De-identified claims data for commercially insured patients in the IQVIA PharMetrics® Plus US database (Jan-2006 to Jun-2015) were extracted. Eligible patients had ≥2 claims for VWD (ICD-9 code 286.4), and continuous health-plan enrolment for ≥2 years before and after diagnosis. Bleeding event, treatment and treating-physician type were analysed for 18 months before and 7-24 months after diagnosis, according to pre-diagnosis bleeding phenotype (claims from one vs multiple bleed sites) and post-diagnosis bleeding status (resolved [no post-diagnosis bleed claims] vs continued [≥1 claim]).

Data for 3756 eligible patients (72.6% female; 71.0% aged ≥18 years at diagnosis) were analysed. Overall, 642 (17.1%) and 805 (21.4%) patients had single- and multiple-site bleed claims pre-diagnosis, respectively, and 1263 (33.6%) patients (38.5% of women, 20.8% of men) continued to bleed post-diagnosis. Multiple-site bleeding was associated with pre-diagnosis heavy menstrual bleeding (HMB), oral contraceptive (OC) use and nasal cauterization. Continued bleeding post-diagnosis was associated with pre-diagnosis gastrointestinal bleeding, HMB and epistaxis; pre-diagnosis use of OCs, aminocaproic acid and nasal cauterization; and younger age at diagnosis. Few patients consulted a haematologist for bleed management.

Many patients with VWD have persistent bleeding from multiple sites and continue to bleed post-diagnosis. Our findings suggest a need to optimize management to reduce the symptomatic burden of VWD following diagnosis.
Many patients with VWD have persistent bleeding from multiple sites and continue to bleed post-diagnosis. Our findings suggest a need to optimize management to reduce the symptomatic burden of VWD following diagnosis.
The COVID-19 pandemic has resulted in lifestyle changes for children. The aim of this study was to evaluate the impact of the pandemic on weight/BMI in children with severe bleeding disorders.

We conducted a retrospective review of patients age 3-18 years with severe bleeding disorders on prophylactic therapy treated at SickKids Hospital (Toronto, Canada) between February 01, 2018 and March 31, 2021. We evaluated the following pre- and post-COVID variables weight (kg), weight percentile, BMI (kg/m
), BMI percentile, HJHS score, and prophylactic dosing (units/kg).

One hundred and four patients were included in the final analysis.Diagnoses were as followshaemophilia A (n=92; 70.8%), haemophilia B (n=17; 13.1%), type 3 von Willebrand disease (n=11; 8.5%), the remainder were diagnosed with rare factor deficiencies.Median interval time from pre-COVID measurements to latest follow-up was 12.4 months (IQR 10.32-14.52 months) during which there was a statistically significant increase in median weight percentile +5.75 centiles (from 63
centile to 68.75
centile).There was a statistically significant increase in mean BMI of +1.03kg/m
(P=<.001) while median BMI percentile increased +8.82 centiles (from 53.9
centile to 62.72
centile) and mean BMI percentile increased 3.42 centiles (from 57.5 centile to 60.9 centile).The group that gained the most weight centiles, BMI and BMI centiles were 5-14 years old.

There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.
There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.This study aimed to evaluate the influence of sterilization methods on conventional and bulk-fill resin composites' (BFRCs) surface properties in an attempt to preview bias in laboratory bacterial adhesion tests. Two regular viscosity conventional resin composites [Filtek Z350 XT™ (Z350) and IPS Empress Direct™ (ED)] and two regular viscosity BFRCs [Filtek Bulk Fill™ (FILT) and Tetric N-Ceram Bulk Fill IVA™ (TBF)] were used. The materials were characterized by Scanning Electron Microscopy (SEM), surface roughness (SR), and wettability (W) after sterilization with hydrogen peroxide gas plasma (HPGP) and steam sterilization (SS). Nonsterilized samples served as a control group (n = 5). Statistical analysis was performed using two-way analysis of variance (ANOVA) and Tukey post hoc test (p  .05). SS method decreased the contact angle for FILT and Z350 (p  less then  .01). The SS promoted more exposition of filler particles, while the HPGP method did not alter the tested materials' morphology. Therefore, sterilization methods affected the resin composites tested selectively. HPGP seems to be the most recommended method to sterilize the tested resin composites before laboratory bacterial adhesion tests.
The benefits of clinical practice guideline (CPG) adoption for the management of patients with back pain are well documented. However, the gap between knowledge creation and implementation remains wide with few studies documenting the iterative process of comprehensive implementation in clinical settings. The objective of this study was to improve adherent physical therapy care according to CPG's for low back pain and describe the knowledge to action (K2A) process used in a rural healthcare organization.

A prospective case control cohort design was used to evaluate physical therapy provider practice changes during an 18 month intervention. Four clinical sites were selected, two of which received multifaceted educational and process interventions tailored to feedback from ongoing K2A cycle outcomes. Overall program assessment included monthly charge code reports for adherence and a pre-post survey of confidence for guideline use. Pragmatic Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) crarisons, long-term reporting and standardized frameworks for assessment of real-world CPG implementation.
This study extends the literature of guideline implementation by describing the unique cycles required for promoting provider behaviour change within a rural healthcare system. Adherence and confidence results suggest increased provider CPG use which was supported by the process evaluation. This study demonstrates the importance of multiple site comparisons, long-term reporting and standardized frameworks for assessment of real-world CPG implementation.The helical sense control of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) is greatly affected when they are conjugated to AuNPs through a strong thiol-Au connection, which restricts conformational changes at the polymer. Thus, the classical thiol-MNP bonds must be replaced by weaker ones, such as supramolecular amide-Au interactions. A straightforward preparation of the PPA-Au nanocomposite by reduction of a preformed PPA-Au3+ complex cannot be used due to a redox reaction between the two components of the complex which degrades the polymer. To avoid the interaction between the PPA and the Au3+ ions before the reduction takes place, the metal ions are added to the polymer solution capped as a TOAB complex, which keeps the PPA stable due to the lack of PPA-Au3+ interactions. Ulterior reduction of the Au3+ ions by NaBH4 affords the desired nanocomposite, where the AuNPs are stabilized by supramolecular anilide-AuNPs interactions. By using this approach, 3.7 nm gold nanoparticles are generated and aligned along the polymer chain with a regular distance between particles of 6 nm that corresponds to two helical pitches. These nanocomposites show stimuli-responsive properties and are also able to form macroscopically chiral nanospheres with tunable size.SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four SEC24 paralogs (A-D) in vertebrates, which are classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans. sec24d mutant fish also recapitulate the phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient-derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. Using Sec24d KO mice and cultured cells, we show that SEC24A and SEC24B also contribute to endoplasmic reticulum (ER) export of procollagen. In contrast, fibronectin 1 requires either SEC24C or SEC24D for ER export. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.
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