Early Impressions and Adoption of the AtriAmp for Managing Arrhythmias Following Congenital Heart Surgery.

Objective: AtriAmp is a new medical device that displays a continuous real-time atrial electrogram on telemetry using temporary atrial pacing leads. Our objective was to evaluate early adoption of this device into patient care, understand how it affected clinical workflow, and identify unforeseen benefits or limitations. Design: Qualitative study using inductive analysis of semi-structured interviews to identify dominant themes. Setting: Single center, tertiary, academic 21-bed mixed pediatric intensive care unit (PICU). Subjects: PICU multidisciplinary team members (Pediatric intensivists, PICU Nurse Practitioners, PICU nurses and Pediatric Cardiologists) who were early adopters of the AtriAmp (n=14). Results: Three prominent themes emerged from qualitative analysis of the early adopters' experiences. (1) Accelerated time from arrhythmia event to diagnosis, treatment, and determination of treatment effectiveness; (2) Increased confidence and security in the accuracy of providers' arrhythmia diagnosis; and (3) Improvement in the ability to educate providers about post-operative arrythmias where reliance on time consuming consultation is a default. Providers also noted some learning curves with the device; none of which compromised medical care or clinical workflow. Conclusions: Insights from early adopters of AtriAmp signal the need for simplicity and fidelity in new technologies within the PICU. Further research in the qualitative and observational sphere is needed to understand how technologies, such as AtriAmp, find expanded use in the PICU environment. Our research suggests that such technologies can be pivotal to the support and growth of multi-disciplinary teams, even among those who do not participate in early implementation.

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

The prevalence of JAK2 exon12 mutations in Vietnamese patients with JAK2 V617F-negative polycythemia vera: frequent or rare?

Purpose Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of Polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among Polycythemia Vera patients in Vietnam has not been studied yet. Objectives The overall study objective is to investigate the frequency of JAK2 exon 12 mutations among V617F-negative Polycythemia Vera patients in Vietnam. Methods In this study, the occurrence of these mutations was investigated in a clinical population of 76 Vietnamese Polycythemia Vera patients by PCR-RFLP and Sanger sequencing. Results The result showed that 53 of the patients were V617F-positive, and in 23 V617F-negative patients, only four individuals carried two JAK2 exon 12 mutations. Analysis by different in-silico tools predicted that all the two exon 12 mutations detected in this study (JAK2 c.1592A>G; p.H531R and c.1616A>G p.K539R) were benign. Conclusion These results suggested that the causative mutations in this V617F-negative subgroup might locate in another genetic region, and mutations in exon 12 might not be as common among the V617F-negative Polycythemia Vera patients as thought.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Copper Binding Regulates Cellular Prion Protein Function.

The cellular prion protein (PrPC), mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neuritogenesis. In addition, its ability to bind copper or zinc has been suggested for its role in metal homeostasis. Although PrPC has been known as a copper-binding molecule, little is known about how copper can affect PrPC physiological functions. By combining genomic approaches, cellular assays, and focal stimulation technique, we found that PrPC neuritogenesis function is directly influenced by N-terminal copper-binding amino acids. Several recombinant mouse PrP (recMoPrP) mutants at N-terminal copper-binding sites were produced, and primary hippocampal cultures were treated either in bulk or exposed near the hippocampal growth cones (GC) of single neurons in local stimulation manner. While focal stimulation of GC with wild-type recMoPrP induced neurite outgrowth and rapid GC turning toward the source, N-terminal mutants fail to support this effect. Indeed, disrupting all the copper-binding sites at the N-terminus of PrPC was toxic to neurons indicating that these regions are crucial for the protein function. Mutants at both octarepeat and non-octarepeat region abolished the neuritogenesis effect. Altogether, our findings indicate the crucial role of copper-binding sites in maintaining the neuritogenesis function in PrP, suggesting a potential link between loss-of-function of the protein and disease initiation.

Characterization of prion protein function by focal neurite stimulation.

The cellular prion protein (PrPC), encoded by the PRNP gene, is a ubiquitous glycoprotein, which is highly expressed in the brain. This protein, mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neurite outgrowth. By using a novel focal stimulation technique, we explored the potential function of PrPC, in its soluble form, as a signaling molecule. Thus, soluble recombinant prion proteins (recPrP) encapsulated in micro-vesicles were released by photolysis near the hippocampal growth cones. Local stimulation of wild-type growth cones with full-length recPrP induced neurite outgrowth and rapid growth cone turning towards the source. This effect was shown to be concentration dependent. Notably, PrPC-knockout growth cones were insensitive to recPrP stimulation, but this property was rescued in PrP-knockout growth cones expressing GFP-PrP. Taken together, our findings indicate that recPrP functions as a signaling molecule, and that its homophilic interaction with membrane-anchored PrPC might promote neurite outgrowth and facilitate growth cone guidance.

The Guinness molecules for the carbohydrate formula.

A systematic review and analysis of the most stable spatial arrangements of n carbon, n oxygen, and 2n hydrogen atoms including vibrational zero-point energy up to n = 5 shows that small-molecule aggregates win, typically followed by thermally unstable molecules, before kinetically stable molecules and finally carbohydrates are found. Near n ≈ 60 a crossover to carbon allotropes and ice as the global minimum structure is expected and the asymptotic limit is most likely graphite and ice. Implications for astrochemical and fermentation processes are discussed. Density functionals like B3LYPD3 are found to describe these energy sequences quite poorly, mostly due to an overestimated stability of carbon in high oxidation states.

The current impact of entry-level associate and baccalaureate degree education on the diversity of respiratory therapists.

INTRODUCTION: Transitioning from an associate degree to a baccalaureate degree for respiratory therapists has been suggested as a new entry-level educational standard. One potential risk for this change is that it may limit the diversity of potential applicants for entry-level education. A diverse workforce is important to achieve the goal of reducing healthcare disparities. This study evaluated characteristics of therapists who completed associate and baccalaureate degree entry-level education. METHODS: A secondary analysis of data collected from the 2009 AARC Respiratory Therapist Human Resource Survey explored relationships between the choice of entry-level associate or baccalaureate education and variables of gender, race, salary, career advancement, and job satisfaction. RESULTS: There were no differences between therapists with entry-level associate and baccalaureate degrees in gender, race, number of additional healthcare credentials, numbers of life support credentials, wages, delivering respiratory care by protocol, and job satisfaction. There were significantly higher percentages of advanced academic degrees, desire to pursue a higher academic degree, registered respiratory therapist credentials, total National Board for Respiratory Care credentials, and leadership roles for therapists with baccalaureate entry-level degrees. CONCLUSIONS: Current entry-level associate and baccalaureate degree graduates have similar gender and race proportions. This finding challenges concerns that an entry-level baccalaureate degree would decrease the diversity of the respiratory therapist workforce.