Circle Time Health Curriculum Designed for Pre-Schoolers

Introduction. Over 20% of low-income, Head Start eligible children are not up to date on regular healthcare exams. While many barriers exist in ensuring universal access and compliance with standard healthcare visits for young children, we sought to educate children about physician’s practices in order to engage and integrate their involvement and understanding of their well-being.https://scholarworks.uvm.edu/comphp_gallery/1197/thumbnail.jp

Phase Coherence as a Measure of Acoustic Quality, part two: Perceiving Engagement

ABSTRACT The first of these three papers described the physics and physiology that enables humans to detect nearly instantly the apparent closeness of a sound source. In this section we describe some of the research that forms the basis for many of the myths that govern the use of early reflections in current hall designs, and the personal experiences that lead the author to question these myths. With the help of many fine artists, musicians and engineers I learned to hear how the apparent closeness of a sound directs the brain to pay close attention -and thus the degree of engagement we have in a performance of drama or music. Together these experiences constitute a plea for acoustic designs that encourage engagement over a wide range of seats. Since engagement and the clarity of both speech and music are closely related, this plea is really asking that we design halls where all the notes can be heard. Composers will thank us

Semienzymatic cyclization of disulfide-rich peptides using sortase A

Background: Sortase A (SrtA) is a transpeptidase capable of catalyzing the formation of amide bonds. Results: SrtA was used to backbone-cyclize disulfide-rich peptides, including kalata B1, -conotoxin Vc1.1, and SFTI-1. Conclusion: SrtA-mediated cyclization is applicable to small disulfide-rich peptides. Significance: SrtA-mediated cyclization is an alternative to native chemical ligation for the cyclization of small peptides of therapeutic interest

Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial

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A Method for Structure–Activity Analysis of Quorum-Sensing Signaling Peptides from Naturally Transformable Streptococci

Many species of streptococci secrete and use a competence-stimulating peptide (CSP) to initiate quorum sensing for induction of genetic competence, bacteriocin production, and other activities. These signaling molecules are small, unmodified peptides that induce powerful strain-specific activity at nano-molar concentrations. This feature has provided an excellent opportunity to explore their structure–function relationships. However, CSP variants have also been identified in many species, and each specifically activates its cognate receptor. How such minor changes dramatically affect the specificity of these peptides remains unclear. Structure–activity analysis of these peptides may provide clues for understanding the specificity of signaling peptide–receptor interactions. Here, we use the Streptococcus mutans CSP as an example to describe methods of analyzing its structure–activity relationship. The methods described here may provide a platform for studying quorum-sensing signaling peptides of other naturally transformable streptococci

Policy solutions to improve access to fertility treatment and optimise patient care: consensus from an expert forum

BackgroundInfertility is an underrecognized disease which affects over 17% of the reproductive age population worldwide. However, availability of, and access to, assisted reproductive technology (ART) is variable across countries. There are significant challenges relating to awareness, financial and other barriers to care, cultural considerations, and the level of support provided to people undergoing care. Previous studies have explored these challenges, but less attention has been given to the policy implications. As the need for fertility care rises, we investigate the evidence that policy changes can be implemented to improve access to ART treatment.MethodsA review of literature was conducted on fertility policy challenges and developments, covering fertility recognition and awareness; cultural and religious considerations; and access to ART treatment, psycho-social care, and supplementary care. Nine medical and academic experts were invited to validate secondary research findings and provide their perspectives on policy implications. The experts covered different specialties and geographic expertise. Experts participated in individual 60-minute interviews, then a half-day Policy Forum discussion was held virtually in May 2023.ResultsLack of recognition of infertility as a disease, low financial coverage of fertility services, limited psychosocial support, and cultural considerations are substantial barriers to fertility services access. Some countries have limited reimbursement of services or offer only private care, significantly limiting treatment access. Others restrict reimbursement based on age, gender and family status, which creates access inequities. Policy action is needed to mitigate these challenges and to ensure timely and equitable access to fertility care. Decision-makers need to collectively recognize infertility as a disease, rather than just a social issue. Equity of access to infertility services should be ensured by expanding the availability of public funding, along with review and rationalisation of criteria for treatment reimbursement. To improve engagement in treatment and support through the fertility journey, access to psychosocial care should be expanded and included as a core service.ConclusionMajor obstacles to accessing ART treatment have been identified across regions globally, highlighting the urgent need for national policy action to enhance care quality by reviewing current legislation, improving patient and physician education, refining reimbursement procedures, and expanding psychosocial support services

RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m(2) every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m(2) daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade >= 3 related treatment-emergent adverse events (TEAEs). The most common grade >= 3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged

Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence

Using assay-directed fractionation of Conus geographus crude venom, we isolated a-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective alpha-conotoxins, alpha-GID has a four amino acid N-terminal tail, gamma-carboxyglutamate (Gla), and hydroxyproline (0) residues, and lacks an amidated C terminus. GID inhibits alpha7 and alpha3beta2 nAChRs with IC50 values of 5 and 3 nm, respectively and is at least 1000-fold less potent at the alpha1beta1gammadelta, alpha3beta4, and alpha4beta4 combinations. GID also potently inhibits the alpha4beta2 subtype (IC50 of 150 nm). Deletion of the N-terminal sequence (GIDDelta1-4) significantly decreased activity at the alpha4beta2 nAChR but hardly affected potency at alpha3beta2 and alpha7 nAChRs, despite enhancing the off-rates at these receptors. In contrast, Arg(12) contributed to alpha4beta2 and alpha7 activity but not to alpha3beta2 activity. The three-dimensional structure of GID is well defined over residues 4-19 with a similar motif to other a-conotoxins. However, despite its influence on activity, the tail appears to be disordered in solution. Comparison of GID with other alpha4/7-conotoxins which possess an NN(P/O) motif in loop II, revealed a correlation between increasing length of the aliphatic side-chain in position 10 (equivalent to 13 in GID) and greater alpha7 versus alpha3beta2 selectivity