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.

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.

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.

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.

Toward a Global Genomic Epidemiology of Meningococcal Disease.

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.

Biocompatible Soft Fluidic Strain and Force Sensors for Wearable Devices.

Fluidic soft sensors have been widely used in wearable devices for human motion capturing. However, thus far, the biocompatibility of the conductive liquid, the linearity of the sensing signal, and the hysteresis between the loading and release processes have limited the sensing quality as well as the applications of these sensors. In this paper, silicone based strain and force sensors composed of a novel biocompatible conductive liquid (potassium iodide and glycerol solution) are introduced. The strain sensors exhibit negligible hysteresis up to 5 Hz, with a gauge factor of 2.2 at 1 Hz. The force sensors feature a novel multi-functional layered structure, with micro-cylinder-filled channels to achieve high linearity, low hysteresis (5.3% hysteresis at 1 Hz), and good sensitivity (100% resistance increase at a 5 N load). The sensors' gauge factors are stable at various temperatures and humidity levels. These bio-compatible, low hysteresis, and high linearity sensors are promising for safe and reliable diagnostic devices, wearable motion capture, and compliant human-computer interfaces.

Outbreak of scabies among preschool children, Accra, Ghana, 2017.

BACKGROUND: Scabies occurs worldwide with a prevalence between 0.3 and 46.0%. In Ghana, even though a 5.1% proportion of scabies was reported in a retrospective review of skin diseases at the Korle Bu Teaching Hospital, the nationwide prevalence of scabies is unknown. Overall, its burden is higher in tropical regions. Scabies outbreaks mostly occur among children, the elderly in nursing homes, and prison inmates. Even though primary scabies hardly results in mortalities, the pain, itch, and systemic complications from secondary bacterial infections account for about 1.5 million years lived with disabilities. We investigated a scabies outbreak among school children in Ghana to determine its magnitude, stop the outbreak, and institute preventive measures to minimize risks of future outbreaks. METHODS: The investigation was conducted between March 14 and May 17, 2017 among pupils of Presbyterian Secondary Staff Basic School in Accra. We defined a case as a school child who on clinical examination, had an intensely pruritic rash on at least one typical predilection site with or without a burrow, or positive skin scrapings on microscopy. We screened and line listed cases, performed laboratory investigations on skin scrapings and wound swaps, and conducted an environmental assessment. We performed descriptive statistics on data, and calculated attack rate ratios (ARR) at 95% confidence level. RESULTS: Of 823 preschool children screened, 92 were cases. Median age of cases was 4 years (range 2-7 years) and their modal age was 3 years. The overall attack rate was 11.2% (92/823). The sex specific attack rate was 11.5% for males, and 10.8% for females (ARR: 0.93; CI: 0.67-1.28). Compared with the least affected class (crèche), the nursery one class was worst affected (ARR: 5.14; CI: 3.44-7.50). On microscopy, all skin scrapings were negative for scabies. Staphylococcus aureus and Streptococcus spp. were isolated from secondarily infected scabies lesions. CONCLUSIONS: A scabies outbreak with a propagated source occurred among preschool children. The 3-year-old pupils were most affected. It was controlled by mass treatment with benzyl benzoate and health education. Classrooms and sleeping mats were disinfected. We recommended the decongestion of classrooms and discouraged sharing of sleeping mats.

Solvent- and Pressure-Induced Phase Changes in Two 3D Copper Glutarate-Based Metal-Organic Frameworks via Glutarate (+gauche ⇄ -gauche) Conformational Isomerism.

Two isoreticular three-dimensional copper(II) glutarate-based pillared-layered metal-organic frameworks (MOFs) with flexible pillars, [Cu2(glu)2(bpa)] and [Cu2(glu)2(bpp)] (bpa = 1,2-bis(4-pyridyl)ethane; bpp = 1,3-bis(4-pyridyl)propane), undergo spontaneous phase changes upon solvent loss at room temperature. Using single-crystal X-ray diffraction analysis (SCXRD), we show that the phase changes result in new narrow-channel forms that experience a large reduction in solvent-accessible volume. Moreover, the [Cu2(glu)2(bpa)] MOF displays a stepped sorption isotherm for the uptake of CO2 at room temperature. This is indicative of reversion of the framework to the wide-channel form under CO2 pressure. Supercritical CO2 was used to isolate the gas-included structures, and by means of SCXRD we were able to determine the positions of the CO2 molecules in the channels of the frameworks. Finally, we report the use of molecular modeling simulations to elucidate the phase-change mechanism, including the energetic changes involved. Structural limitations in both MOFs allow for only direct gauche-gauche enantiomeric interconversion of the glutarate moieties.

Solid-State Conformational Flexibility at Work: Zipping and Unzipping within a Cyclic Peptoid Single Crystal.

A peptidomimetic compound undergoes a reversible single-crystal-to-single-crystal transformation upon guest release/uptake with the transformation involving a drastic conformational change. The extensive and reversible alteration in the solid state is connected to the formation of an unprecedented "CH-π zipper" which can reversibly open and close (through the formation of CH-π interactions), thus allowing for guest sensing.

Giant Negative Area Compressibility Tunable in a Soft Porous Framework Material.

A soft porous material [Zn(L)2(OH)2]n·Guest (where L is 4-(1H-naphtho[2,3-d]imidazol-1-yl)benzoate, and Guest is water or methanol) exhibits the strongest ever observed negative area compressibility (NAC), an extremely rare property, as at hydrostatic pressure most materials shrink in all directions and few expand in one direction. This is the first NAC reported in metal-organic frameworks (MOFs), and its magnitude, clearly visible and by far the highest of all known materials, can be reversibly tuned by exchanging guests adsorbed from hydrostatic fluids. This counterintuitive strong NAC of [Zn(L)2(OH)2]n·Guest arises from the interplay of flexible [-Zn-O(H)-]n helices with layers of [-Zn-L-]4 quadrangular puckered rings comprising large channel voids. The compression of helices and flattening of puckered rings combine to give a giant piezo-mechanical response, applicable in ultrasensitive sensors and actuators. The extrinsic NAC response to different hydrostatic fluids is due to varied host-guest interactions affecting the mechanical strain within the range permitted by exceptionally high flexibility of the framework.

Macroparasites of introduced parakeets in Italy: a possible role for parasite-mediated competition.

Alien species are considered a cause of biodiversity loss throughout the world. An important but often overlooked form of competition with native species is the parasite-mediated one. Introduced species may bring their own parasites from their native ranges (spillover) or get native parasites from native species, thus increasing the parasites' spread and transmission risk (spillback). Thus, a complete knowledge of parasites hosted by introduced species is important to assess and to possibly prevent impacts. Ring-necked and monk parakeets have been introduced in many European countries, where they established a number of alien reproductive populations. We sampled 21 ring-necked parakeets and 7 monk parakeets from Italy and identified 35 arthropod ectoparasites belonging to five species. Amongst those, one species was native to India (Neopsittaconirmus lybartota), where alien populations of ring-necked parakeet may have been originated, and one species from South America (Paragoniocotes fulvofasciatus), which is typically found of the monk parakeet in its native range. The other three species of arthropod parasites were native to Italy and commonly found on native species, suggesting the possibility of spillback processes.

Characterisation of microsatellite loci in two species of lice, Polyplax serrata (Phthiraptera: Anoplura: Polyplacidae) and Myrsidea nesomimi (Phthiraptera: Amblycera: Menoponidae).

Polymorphic microsatellite loci were characterised for two louse species, the anopluran Polyplax serrata Burmeister, 1839, parasitising Eurasian field mice of the genus Apodemus Kaup, and the amblyceran Myrsidea nesomimi Palma et Price, 2010, found on mocking birds endemic to the Galápagos Islands. Evolutionary histories of the two parasites show complex patterns influenced both by their geographic distribution and through coevolution with their respective hosts, which renders them prospective evolutionary models. In P. serrata, 16 polymorphic loci were characterised and screened across 72 individuals from four European populations that belong to two sympatric mitochondrial lineages differing in their breadth of host-specificity. In M. nesomimi, 66 individuals from three island populations and two host species were genotyped for 15 polymorphic loci. The observed heterozygosity varied from 0.05 to 0.9 in P. serrata and from 0.0 to 0.96 in M. nesomimi. Deviations from the Hardy-Weinberg equilibrium were frequently observed in the populations of both parasites. Fst distances between tested populations correspond with previous phylogenetic data, suggesting the microsatellite loci are an informative resource for ecological and evolutionary studies of the two parasites.

Extreme carbon dioxide sorption hysteresis in open-channel rigid metal-organic frameworks.

A systematic study is presented of three closely related microporous metal-organic frameworks the pore dimensions of which vary according to the choice of 4,4'-bipyridyl linker. The tunable linker allows exploration of the effect of increasing pore dimensions on the sorption behavior of the frameworks. The MOFs described capture CO2 under supercritical conditions and continue to sequester the gas under ambient conditions. Gas sorption isotherms for CO2 are compared with thermogravimetric data, and the CO2 molecules in the channels of the frameworks could be modeled using single-crystal X-ray diffraction analysis. Crystallographic data were used to construct a theoretical model based on DFT methods to calculate framework electrostatic potential maps with a view to understanding the nature of the sorbate-sorbent interactions.

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated ß-cyclodextrins: models for cyclodextrin-steroid interaction.

The interaction between the potent anticancer agent 2-methoxyestradiol (2ME) and a series of cyclodextrins (CDs) was investigated in the solid state using thermal analysis and X-ray diffraction, while the possibility of enhancing its poor aqueous solubility with CDs was probed by means of equilibrium solubility and dissolution rate measurements. Single crystal X-ray diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-ß-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-ß-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion complexation invariably involves insertion of the D-ring of 2ME from the secondary side of each CD molecule, with the 17-OH group generally hydrogen bonding to a host glycosidic oxygen atom within the CD cavity, while the A-ring and part of the B-ring of 2ME protrude from the secondary side. In the case of the TRIMEB·2ME complex, there is evidence that complexation proceeds with mutual conformational adaptation of host and guest molecules. The aqueous solubility of 2ME was significantly enhanced by CDs, with DIMEB, TRIMEB, randomly methylated ß-CD and hydroxypropyl-ß-CD being the most effective hosts. The 2:1 host-guest ß-CD inclusion complex, prepared by two methods, yielded very rapid dissolution in water at 37 °C relative to untreated 2ME, attaining complete dissolution within 15 minutes (co-precipitated complex) and 45 minutes (complex from kneading).

Accurate whole human genome sequencing using reversible terminator chemistry.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.

SR450 And Superhawk XP Applications Of Bacillus thuringiensis israelensis Against Culex quinquefasciatus.

Sprayer comparisons and larval morality assays were conducted following SR450 backpack mist blower and Superhawk XP thermal fogger applications of Vectobac® WDG Bacillus thuringiensis israelensis (Bti) against Culex quinquefasciatus. Bacillus thuringiensis israelensis was applied at maximum label rate in a 232.26-m(2) field plot located in north-central Florida with containers placed at 2 heights (ground level and 1.52 m above ground) on stakes positioned 3.04, 6.09, 9.14, 12.19, and 15.24 m from the spray line. Results indicated that there was no significant (P > 0.05) difference in 24- and 48-h larval mortality between the 2 sprayers or between the 2 heights. There was significant difference (P < 0.05) among the 5 rows, with mortality continuously decreasing with increasing distance from sprayer. Both sprayers provided on average >70% larval mortality 3.04-9.14 m from the spray line, and <60% mortality at 12.19 and 15.24 m. The data suggest that the SR450 and Superhawk XP may be comparable sprayers for use with Bti to control mosquito larvae.

Tunable anisotropic thermal expansion of a porous zinc(II) metal-organic framework.

A novel three-dimensional metal-organic framework (MOF) that displays anisotropic thermal expansion has been prepared and characterized by single-crystal X-ray diffraction (SCD) and thermal analysis. The as-prepared MOF has one-dimensional channels containing guest molecules that can be removed and/or exchanged for other guest molecules in a single-crystal to single-crystal fashion. When the original guest molecules are replaced there is a noticeable effect on the host mechanics, altering the thermal expansion properties of the material. This study of the thermal expansion coefficients of different inclusion complexes of the host MOF involved systematic alteration of guest size, i.e., methanol, ethanol, n-propanol, and isopropanol, showing that fine control over the thermal expansion coefficients can be achieved and that the coefficients can be correlated with the size of the guest. As a proof of concept, this study demonstrates the realizable principle that a single-crystal material with an exchangeable guest component (as opposed to a composite) may be used to achieve a tunable thermal expansion coefficient. In addition, this study demonstrates that greater variance in the absolute dimensions of a crystal can be achieved when one has two variables that affect it, i.e., the host-guest interactions and temperature.

Preterm infant swallowing of thin and nectar-thick liquids: changes in lingual-palatal coordination and relation to bolus transit.

Tongue-soft palate coordination and bolus head pharyngeal transit were studied by means of postacquisition kinematic analysis of videofluoroscopic swallowing images of ten preterm infants referred from hospital NICUs due to poor oral feeding and suspicion of aspiration. Sequences of coordinated tongue-soft palate movements and bolus transits during swallows of thin-consistency and nectar-thick-consistency barium were digitized, and time series data were used to calculate continuous relative phase, a measure of coordination. During swallows of nectar-thick compared to thin barium, tongue-soft palate coordination was more likely to be antiphase, bolus head pharyngeal transit time was longer, and coordination was significantly correlated with bolus head pharyngeal transit. Analysis of successive swallows indicated that tongue-soft palate coordination variability decreased with nectar-thick but not with thin-consistency barium. Together, the results suggest that slower-moving bolus transits may promote greater opportunity for available sensory information to be used to modulate timing of tongue-soft palate movements so that they are more effective for pumping liquids.