Mechanochemically-Assisted Passerini Reactions: A Practical and Convenient Method for the Synthesis of Novel α-Acyloxycarboxamide Derivatives.

A carboxylic acid, an aldehyde, and an isonitrile were combined in a single step (Passerini reaction) under mechanochemical activation to produce several α-acyloxycarboxamide derivatives in high to excellent yields within 15 min of milling. Mechanochemistry, when combined with the diversity provided by multicomponent reactions, enables the efficient synthesis of the target compounds, with great atom economy, shorter reaction times, and experimental simplicity. The method allows for the rapid production of a vast library of complex compounds from a limited number of substrates.

N-Formamide as a carbonyl precursor in the catalytic synthesis of Passerini adducts under aqua and mechanochemical conditions.

A new simple, efficient, and environmentally friendly protocol is presented for the catalytic synthesis of α-acyloxycarboxamides using N-formamides as a carbonyl precursor under aqua and mechanochemical conditions. Immobilized sulfuric acid on silica gel was employed for the synthesis of desired products, via the reaction of benzoic acid, 1-napthylisocyanide and various heterocyclic N-formamides. After a careful optimization of the reaction conditions, the desired Passerini products were obtained in high to excellent yields in short reaction times (10-30 min) at room temperature. The highly efficient and environmentally friendly method provides a facile access to a library of α-acyloxycarboxamides derivatives for future research on bioactivity screening.

Aqua/Mechanochemical Mediated Synthesis of Novel Spiro [Indole-Pyrrolidine] Derivatives.

Spirocyclic scaffolds are found in many pharmacologically active natural and synthetic compounds. From time to time, efforts have been made to develop new or better processes for the synthesis of spirocyclic compounds. Spiro [Indole-pyrrolidine] Derivatives are readily synthesized in high to excellent yields by the Michael condensation of 3-dicyanomethylene-2H-indol-2-ones (produced via the Knoevenagel condensation of indole-2,3-dione with malononitrile) with isothiocyanate derivatives under aqueous and mechanochemical conditions. The advantages of this protocol are that the reactions are solvent-free, occur at ambient temperature, require short reaction times, have experimental simplicity, and produce excellent yields. These environmentally friendly reaction media are useful alternatives to volatile organic solvents.

RSV-related hospitalization and outpatient palivizumab use in very preterm (born at <29 wGA) infants: 2003-2020.

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.

NICU discharge preparation and transition planning: guidelines and recommendations.

In this section, we present Interdisciplinary Guidelines and Recommendations for Neonatal Intensive Care Unit (NICU) Discharge Preparation and Transition Planning. The foundation for these guidelines and recommendations is based on existing literature, practice, available policy statements, and expert opinions. These guidelines and recommendations are divided into the following sections: Basic Information, Anticipatory Guidance, Family and Home Needs Assessment, Transfer and Coordination of Care, and Other Important Considerations. Each section includes brief introductory comments, followed by the text of the guidelines and recommendations in table format. After each table, there may be further details or descriptions that support a guideline or recommendation. Our goal was to create recommendations that are both general and adaptable while also being specific and actionable. Each NICU's implementation of this guidance will be dependent on the unique makeup and skills of their team, as well as the availability of local programs and resources. The recommendations based only on expert opinion could be topics for future research.

NICU discharge preparation and transition planning: introduction.

The National Perinatal Association (NPA) coordinated a multidisciplinary work group to develop guidelines and recommendations for Neonatal Intensive Care Unit (NICU) discharge preparation and thus the transition from NICU to home for infants admitted to the NICU and their families. In this section, we explore the concepts of NICU discharge readiness as well as transition planning and preparation. We describe the process that was used to develop the guidelines and recommendations as well as the timeline for the work. NPA hopes that the readers will find the Interdisciplinary Guidelines and Recommendations for NICU Discharge Preparation and Transition Planning to be beneficial, useful, and pertinent.

The complex Y-chromosomal history of gorillas.

Studies of the evolutionary relationships among gorilla populations using autosomal and mitochondrial sequences suggest that male-mediated gene flow may have been important in the past, but data on the Y-chromosomal relationships among the gorilla subspecies are limited. Here, we genotyped blood and noninvasively collected fecal samples from 12 captives and 257 wild male gorillas of known origin representing all four subspecies (Gorilla gorilla gorilla, G. g. diehli, G. beringei beringei, and G. b. graueri) at 10 Y-linked microsatellite loci resulting in 102 unique Y-haplotypes for 224 individuals. We found that western lowland gorilla (G. g. gorilla) haplotypes were consistently more diverse than any other subspecies for all measures of diversity and comprised several genetically distinct groups. However, these did not correspond to geographical proximity and some closely related haplotypes were found several hundred kilometers apart. Similarly, our broad sampling of eastern gorillas revealed that mountain (G. b. beringei) and Grauer's (G. b. graueri) gorilla Y-chromosomal haplotypes did not form distinct clusters. These observations suggest structure in the ancestral population with subsequent mixing of differentiated haplotypes by male dispersal for western lowland gorillas, and postisolation migration or incomplete lineage sorting due to short divergence times for eastern gorillas.

The impact of policy design on payment concentration in Ad-hoc disaster Relief: Lessons from the Market Facilitation and Coronavirus food Assistance programs.

This study examines the distributional implications of two recent ad-hoc disaster aid programs, the 2018 and 2019 Market Facilitation Payment (MFP) programs that have distinctly different program designs, and the federal crop insurance program. Farm-level data are used to estimate the relationship between farm size, measured by crop sales, and the distribution of program benefits. Results indicate payments are more concentrated on larger farms that receive higher per acre payments under the 2018 MFP and federal crop insurance programs. Under the Coronavirus Food Assistance Program, with a design similar to the 2018 MFP, payments are also more heavily concentrated on larger farms.

Research Infrastructure Contact Zones: a framework and dataset to characterise the activities of major biodiversity informatics initiatives.

Background: The landscape of biodiversity data infrastructures and organisations is complex and fragmented. Many occupy specialised niches representing narrow segments of the multidimensional biodiversity informatics space, while others operate across a broad front, but differ from others by data type(s) handled, their geographic scope and the life cycle phase(s) of the data they support. In an effort to characterise the various dimensions of the biodiversity informatics landscape, we developed a framework and dataset to survey these dimensions for ten organisations (DiSSCo, GBIF, iBOL, Catalogue of Life, iNaturalist, Biodiversity Heritage Library, GeoCASe, LifeWatch, eLTER ELIXIR), relative to both their current activities and long-term strategic ambitions. New information: The survey assessed the contact between the infrastructure organisations by capturing the breadth of activities for each infrastructure across five categories (data, standards, software, hardware and policy), for nine types of data (specimens, collection descriptions, opportunistic observations, systematic observations, taxonomies, traits, geological data, molecular data and literature) and for seven phases of activity (creation, aggregation, access, annotation, interlinkage, analysis and synthesis). This generated a dataset of 6,300 verified observations, which have been scored and validated by leading members of each infrastructure organisation. The resulting data allow high-level questions about the overall biodiversity informatics landscape to be addressed, including the greatest gaps and contact between organisations.

A streamlined workflow for conversion, peer review, and publication of genomics metadata as omics data papers.

BACKGROUND: Data papers have emerged as a powerful instrument for open data publishing, obtaining credit, and establishing priority for datasets generated in scientific experiments. Academic publishing improves data and metadata quality through peer review and increases the impact of datasets by enhancing their visibility, accessibility, and reusability. OBJECTIVE: We aimed to establish a new type of article structure and template for omics studies: the omics data paper. To improve data interoperability and further incentivize researchers to publish well-described datasets, we created a prototype workflow for streamlined import of genomics metadata from the European Nucleotide Archive directly into a data paper manuscript. METHODS: An omics data paper template was designed by defining key article sections that encourage the description of omics datasets and methodologies. A metadata import workflow, based on REpresentational State Transfer services and Xpath, was prototyped to extract information from the European Nucleotide Archive, ArrayExpress, and BioSamples databases. FINDINGS: The template and workflow for automatic import of standard-compliant metadata into an omics data paper manuscript provide a mechanism for enhancing existing metadata through publishing. CONCLUSION: The omics data paper structure and workflow for import of genomics metadata will help to bring genomic and other omics datasets into the spotlight. Promoting enhanced metadata descriptions and enforcing manuscript peer review and data auditing of the underlying datasets brings additional quality to datasets. We hope that streamlined metadata reuse for scholarly publishing encourages authors to create enhanced metadata descriptions in the form of data papers to improve both the quality of their metadata and its findability and accessibility.

Changes in Assessment of and Satisfaction With Discharge Preparation From the Neonatal Intensive Care Unit.

BACKGROUND: A successful transition from the neonatal intensive care unit (NICU) to home is aided by a comprehensive discharge planning program that keeps families involved and engaged with the discharge preparation process. PURPOSE: To compare the assessment of parental NICU discharge preparedness with parental satisfaction with the NICU discharge preparation. METHODS: Families were surveyed 4 to 6 weeks after NICU discharge, and those selecting "very prepared" were considered "satisfied" with their discharge preparation. On discharge day, families were considered "prepared" for discharge based on their overall level of preparedness and their nurse's rating of them on a discharge readiness assessment tool. RESULTS: In total, 1104 families (60%) reported being both "satisfied" and "prepared"; 293 families (16%) were "satisfied" but not "prepared"; 297 families (16%) were not "satisfied" but were "prepared"; and 134 families (7%) were neither "satisfied" nor "prepared." Compared with families that were both "satisfied" and "prepared," families that were neither "satisfied" nor "prepared" were more likely to be raising the infant alone, of Black race, and to have sicker infants. IMPLICATIONS FOR PRACTICE: Some families are at a higher risk and merit more consideration during NICU discharge planning. Assess the discharge readiness of all families prior to discharge. Those at an increased risk may benefit from more discharge education and training, specifically for single mothers, those with limited resources, or others considered at high risk.

High Pressure In Situ Single-Crystal X-Ray Diffraction Reveals Turnstile Linker Rotation Upon Room-Temperature Stepped Uptake of Alkanes.

The rare availability of suitable single-crystal X-ray diffraction (SCXRD) structural data allows for the direct interpretation of the response of a framework to gas sorption and may lead to the development of improved functional porous materials. We report an in situ SCXRD structural investigation of a flexible MOF subjected to methane, ethane, propane, and butane gas pressures. Supporting theoretical investigations indicate weak host-guest interactions for the crystallographically modelled gaseous guests and, in addition, reveal that a turnstile mechanism facilitates the transport of alkanes through the seemingly nonporous system. Inflections present in the adsorption isotherms are furthermore rationalized as due to gate-opening, but without the expected creation of new accessible space.

Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS.

Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer-Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.

Discharge planning considerations for the neonatal intensive care unit.

Neonatal intensive care unit (NICU) discharge readiness is the primary caregivers' masterful attainment of technical care skills and knowledge, emotional comfort and confidence with infant care by the time of discharge. NICU discharge preparation is the process of facilitating discharge readiness. Discharge preparation is the process with discharge readiness as the goal. Our previous work described the importance of NICU discharge readiness and strategies for discharge preparation from an American medical system perspective. NICU discharge planning is, however, of international relevance as challenges in relation to hospital discharge are a recurring global theme. In this manuscript, we conceptualise NICU discharge preparation with international perspective.

Quality by Design Optimization of Cold Sonochemical Synthesis of Zidovudine-Lamivudine Nanosuspensions.

Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato- and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer and the particle size, polydispersity index and Zeta potential determined. Optimization of the nanosuspensions was conducted using a Central Composite Design to produce nano co-crystals with specific identified and desirable Critical Quality Attributes including particle size (PS) < 1000 nm, polydispersity index (PDI) < 0.500 and Zeta potential (ZP) < -30mV. Further characterization was undertaken using Fourier Transform infrared spectroscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry, powder X-ray diffraction and transmission electron microscopy. In vitro cytotoxicity studies revealed that the optimized nano co-crystals reduced the toxicity of AZT and 3TC to HeLa cells.

Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives.

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.