Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index.

PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments.

Screening of castor germplasm for wilt reaction and morpho-molecular characterization of resistant genotypes.

Castor (Ricinus communis L.) is an important industrial versatile non-edible oilseed C3 crop belongs to spurge family. Its oil has exceptional properties which provides an industrial importance to this crop. The present investigation was aimed to evaluate the genotypes of castor for Fusarium wilt reaction in pot followed by characterization of resistant genotypes for yield related traits in field and inter-genotype genetic diversity at DNA level. The percent disease incidence (PDI) among 50 genotypes ranged from 0 to 100%. A total of 36 genotypes were found wilt resistant (28 highly resistant and 8 resistant). ANOVA revealed that the genotypes MSS was significant for each trait studied, indicating the existence of plentiful variability in the experimental material. The morphological characterization showed that DCS-109 (73.30 cm) had a dwarf stature The genotype RG-1954 was superior for oil content (50.29%) with moderate for shelling out (67.63). RG-1673 was outstanding for seed boldness as 100 seed weight for this genotype was maximum (38.98 gm). JI-403 had maximum seed yield per plant (SYPP; 354.88 gm). SYPP positively associated with all traits except oil and seed length:breadth ratio. The path analysis revealed that the direct effects of NPR (0.549), TLFP (0.916), and CPP on SYPP are quite significant. A total of 38 alleles from 18 SSR markers were amplified in 36 genotypes. The NJ tree could divide 36 genotypes into three main clusters. AMOVA revealed 15% and 85% variance among and within subpopulations, respectively. Both morphological and SSR data demonstrated to be effective tools for discerning inter-genotypes diversity and categorizing high-yielding and disesae-tolerant castor genotypes lines.

Metal contamination of soil and translocation in vegetables growing under industrial wastewater irrigated agricultural field of Vadodara, Gujarat, India.

The present investigation was carried out to evaluate metals concentration in ten vegetable crops growing in mixed industrial effluent irrigated agricultural field near Vadodara, Gujarat, India. Differential accumulation and translocation of various metals in selected vegetables plant species was observed. A higher concentration of metals were found in order of Fe>Mn>Zn>Cd>Cu>Pb>Cr>As in soil irrigated with industrial effluent than soil irrigated with tube well water; however, the concentration of As, Cr and Pb found below detection limit in tube well water irrigated soil. Metal accumulation in root and top of vegetables varied significantly both in relations to metal concentration in the soil and the plant genotype. Among ten vegetable species studied five vegetable species, i.e. Spinach, Radish, Tomato, Chili and Cabbage growing in mixed industrial effluent irrigated agricultural field showed high accumulation and translocation of toxic metals (As, Cd, Cr, Pb and Ni) in their edible parts, thus, their cultivation are unsafe with respect to possible transfer in food chain and health hazards. However, it is suggested that vegetable crops restricting toxic metal in non-edible port may be recommended for cultivation in such metal contaminated agricultural field.

Genome-wide microsatellites in amaranth: development, characterization, and cross-species transferability.

Amaranth (Amaranthus spp.) belonging to Amaranthaceae, is known as "the crop of the future" because of its incredible nutritional quality. Amaranthus spp. (> 70) have a huge diversity in terms of their plant morphology, production and nutritional quality; however, these species are not well characterized at molecular level due to unavailability of robust and reproducible molecular markers, which is essential for crop improvement programs. In the present study, 13,051 genome-wide microsatellite motifs were identified and subsequently utilized for marker development using A. hypochondriacus (L.) genome (JPXE01.1). Out of those, 1538 motifs were found with flanking sequences suitable for primer designing. Among designed primers, 225 were utilized for validation of which 119 (52.89%) primers were amplified. Cross-species transferability and evolutionary relatedness among ten species of Amaranthus (A. hypochondriacus, A. caudatus, A. retroflexus, A. cruentus, A. tricolor, A. lividus, A. hybridus, A. viridis, A. edulis, and A. dubius) were also studied using 45 microsatellite motifs. The maximum (86.67%) and minimum (28.89%) cross-species transferability were observed in A. caudatus and A. dubius, respectively, that indicated high variability present across the Amaranthus spp. Total 97 alleles were detected among 10 species of Amaranthus. The averages of major allele frequency, gene diversity, heterozygosity and PIC were 0.733, 0.347, 0.06, and 0.291, respectively. Nei's genetic dissimilarity coefficients ranged from 0.0625 (between A. tricolor and A. hybridus) to 0.7918 (between A. viridis and A. lividus). The phylogenetic tree grouped ten species into three major clusters. Genome-wide development of microsatellite markers and their transferability revealed relationships among amaranth species which ultimately can be useful for species identification, DNA fingerprinting, and QTLs/gene(s) identification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02930-5.

Tablet formulation studies on an oxcarbazepine-beta cyclodextrin binary system.

Oxcarbazepine is a poorly water-soluble (0.083 mg/ml) anti-epileptic drug according to the BCS system (class II) and its dissolution is rate-limiting step for its absorption. The objective of this work was to develop tablet formulations of oxcarbazepine-beta-cyclodextrin (OX-beta-CD) binary systems. Three types of binary systems--physical mixtures, kneaded systems, and coevaporated systems--were studied. Phase solubility studies indicated 1:1 M complexation of oxcarbazepine with beta-cyclodextrin. Drug-beta-CD binary systems were prepared at 1:1 molar ratios and used in formulation studies. The dissolution properties of OX-beta-CD KS (kneaded system, 100.10% drug release in 15 min) were superior than those of the other binary system and pure oxcarbazepine. The tablet formulations containing drug-beta-CD binary systems prepared by wet granulation and direct compression showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Tablet formulations containing drug-beta-CD binary systems prepared by the kneading method showed good dissolution properties (100% drug release in 15 min in direct compression method and 99.9% drug release in 20 min in wet granulation method). Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Accelerated stability studies on some selected tablet formulations were also conducted by keeping the samples at 40 +/- 2 degrees C and 75% relative humidity. There were no statistical differences in the percentage of drug dissolved at 15 and 20 min between fresh and stored samples at the different time points (P < 0.05). Drug content also remained within acceptable limits. Thus, drug-beta-CD binary systems are useful in developing tablet formulations of oxcarbazepine with improved dissolution properties.

Enamel Remineralization with Novel Bioactive Glass Air Abrasion.

Enamel demineralization or white spot lesions (WSLs) are a frequent complication associated with fixed appliance-based orthodontic treatment. The remineralization potential of a novel fluoride-containing bioactive glass (QMAT3) propelled via an air abrasion system was compared with Sylc glass and artificial saliva on artificially induced WSLs. Thirty extracted human premolars were randomly assigned into 3 groups ( n = 10) per method of treatment and scanned with optical coherence tomography and noncontact profilometer in the 4 enamel states: sound, demineralized, after glass propulsion, and after immersion in artificial saliva. Knoop hardness testing was also performed. Twenty additional prepared teeth samples were also randomly selected for examination by scanning electron microscopy and energy-dispersive X-ray spectroscopy (2 teeth per technique) under each of the 4 enamel conditions. 19F MAS-NMR (magic angle spinning-nuclear magnetic resonance) was also used to detect the type of apatite formed on the enamel surface. Significant enamel remineralization with surface roughness and intensity of light backscattering similar to that of sound enamel was observed following treatment with QMAT3. In addition, mineral deposits were detected on the remineralized enamel surfaces, forming a protective layer and improving its hardness. This layer was rich in calcium, phosphate, and fluoride; 19F MAS-NMR confirmed the formation of fluorapatite. This finding is particularly beneficial since fluorapatite is more chemically stable than hydroxyapatite and has greater resistance to acid attack. Hence, a promising fluoride-containing bioactive glass for enamel remineralization has been developed, although further clinical evaluation and refinement is required.

Controlled release of chlorhexidine diacetate from a porous methacrylate system: supercritical fluid assisted foaming and impregnation.

The release of chlorhexidine diacetate (CX) from a self-curing polymeric system based on poly(ethylmethacrylate) and tetrahydrofurfurylmethacrylate (PEM/THFM) was developed in this study. Supercritical fluid assisted impregnation and foaming was employed for preparing porous CX-PEM/THFM drug release system. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) show that the crystallinity of CX significantly decreased after supercritical processing, whilst Raman spectroscopy suggested a hydrogen bonding interaction between the CX and PEM in the product. A UV-Vis dissolution study revealed that the drug release rate is almost as seven times faster in the SCF processed drug delivery system than conventional cured samples.

Genetic analysis of first lactation production traits in Kankrej cattle.

AIM: The aim was to estimate genetic factors affecting the first lactation milk production traits in Kankrej cattle of North Gujarat. MATERIALS AND METHODS: The 475 first lactation records of Kankrej cows that were maintained at the Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat, over a period of 35 years from 1980 to 2014 were studied. The least squares maximum likelihood program was used to estimate genetic parameters of first lactation traits. Heritability was estimated through paternal half-sib analysis in adjusted data. RESULTS: The heritability estimate for production traits was 0.40±0.17, 0.45±0.17, 0.35±0.18, and 0.20±0.14 for standard 300 days milk yield (F300Y), total lactation milk yield (FLY), wet average (FWA), and lactation length (FLL), respectively, in the first parity. All the genetic and phenotypic correlations among different production efficiency traits were high and positive. Genetic correlations between F300Y and FLY, FLL, and FWA were 0.80±0.20, 0.59±0.16, and 0.81±0.32, where as the phenotypic correlations were 0.969, 0.688, and 0.868, respectively. Genetic correlations of FLY with FLL and FWA were 0.60±0.13 and 0.79±0.20, whereas the phenotypic correlations were 0.777 and 0.817, respectively. Genetic and phenotypic correlation between FLL and FWA was 0.63±0.28 and 0.31, respectively. CONCLUSION: The heritability estimate of all first parity lactation traits waslow to medium (0.20-0.45) indicated the scope for further improvement in this trait through selection as well as managemental practice. Higher genetic and phenotypic correlation between thefirst lactation milk production traits gives theidea that genetic gain due to selection for one trait also givesmorecorrelated response of selection for other traits which is economically advantageous.

An apparatus for spatially resolved, temperature dependent reflectance measurements for identifying thermochromism in combinatorial thin film libraries.

A metrology and data analysis protocol is described for high throughput determination of thermochromic metal-insulator phase diagrams for lightly substituted VO2 thin films. The technique exploits the abrupt change in near infrared optical properties, measured in reflection, as an indicator of the temperature- or impurity-driven metal-insulator transition. Transition metal impurities were introduced in a complementary combinatorial synthesis process for producing thin film libraries with the general composition space V(1-x-y)M(x)M'(y)O2, with M and M' being transition metals and x and y varying continuously across the library. The measurement apparatus acquires reflectance spectra in the visible or near infrared at arbitrarily many library locations, each with a unique film composition, at temperatures of 1 °C-85 °C. Data collection is rapid and automated; the measurement protocol is computer controlled to automate the collection of thousands of reflectance spectra, representing hundreds of film compositions at tens of different temperatures. A straightforward analysis algorithm is implemented to extract key information from the thousands of spectra such as near infrared thermochromic transition temperatures and regions of no thermochromic transition; similarly, reflectance to the visible spectrum generates key information for materials selection of smart window materials. The thermochromic transition for 160 unique compositions on a thin film library with the general formula V(1-x-y)M(x)M'(y)O2 can be measured and described in a single 20 h experiment. The resulting impurity composition-temperature phase diagrams will contribute to the understanding of metal-insulator transitions in doped VO2 systems and to the development of thermochromic smart windows.

Site-specific suppression of cell-mediated immunity by cyclosporine.

In this study, it was demonstrated that site-specific suppression of T-cell-mediated immune responsiveness could indeed be achieved by topical application of cyclosporine. Evidence for site-specific immune suppression was obtained from a dual skin allograft model in rats. These animals were given an initial 10-d systemic treatment of CsA. Subsequently, one allograft was treated with topical CsA and the other was treated with the vehicle alone. Anti-inflammatory efficacy and prolonged skin allograft survival were observed both grossly and histopathologically in the presence of topically administered CsA, while contralateral vehicle-treated control grafts underwent vigorous rejection. Systemic lymphocyte DNA synthesis following Con-A and PHA stimulation was normal to elevated. Therefore, systemic T-cell-mediated immunity appeared unaffected or possibly activated even with concomitant topical CsA treatment. CsA levels were low systemically, and showed relative site-specificity in terms of tissue concentration. In conclusion, this study indicates that topical CsA is capable of locally suppressing a strong T-cell-mediated immune response after an initial short-term systemic dose of CsA. Furthermore, certain putative autoimmune and inflammatory diseases of the skin, such as psoriasis and eczematous dermatitis, which may share common mechanisms of action compared to skin allograft rejection should likewise benefit from topical CsA treatment.

Development of stable mixed T cell chimerism and transplantation tolerance without immune modulation in recipients of vascularized bone marrow allografts.

A consistent majority (62.5%) of immunologically unmodified rat recipients transplanted with vascularized hind-limb bone marrow allografts across a semiallogeneic transplant barrier developed tolerance with absence of graft-versus-host disease. A minority of recipients (37.5%) demonstrated lethal GVHD. Transplantation tolerance in the majority was associated with the induction of stable low-level mixed T cell chimerism, including donor CD5+, CD4+, and CD8+ lymphocytes. Chimeras were specifically immune nonresponsive to host alloantigenic determinants. These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention. These vascularized bone marrow transplantation (VBMT) results may establish the experimental foundation for a novel approach to stem cell transfer and bone marrow transplantation.

Cross-linking and ring opening during polymerization of heterocyclic methacrylates and acrylates.

Heterocyclic methacrylates have been shown to have low polymerization shrinkage. In this paper, the extent of ring opening has been assessed by the degree of consequent cross-linking. In polymers of tetrahydrofurfuryl methacrylate and acrylate, tetrahydropyranyl and tetrahydropyran-2-ylmethyl methacrylate, fewer than 1% monomer units were involved in cross-linking and hence ring-opening reactions. 2-epoxypropyl methacrylate, when polymerized, was very extensively cross-linked indicating prolific ring opening. However, the polymerization shrinkage of this material was the highest of the heterocyclic methacrylates studied and was that predicted from the known molar volume change of methacrylate esters. Ring opening does not, therefore, appear to be a significant factor in the polymerization shrinkage of heterocyclic methacrylates.

Heterocyclic methacrylates for clinical applications. I. Mechanical properties.

The mechanical properties of a number of heterocyclic and one cyclic methacrylate have been studied for their potential in low polymerization shrinkage systems. This study included both homopolymers and room temperature polymerizing systems using poly(ethyl methacrylate) powder with a heterocyclic methacrylate monomer. The one cyclic methacrylate studied, isobornyl methacrylate, gave an extremely brittle polymer; furthermore, it would not form a dough with poly(ethyl methacrylate). The homopolymers gave Young's moduli in the range 1.38-2.19 GN/m2, i.e. lower than poly(methyl methacrylate). The moduli of poly(ethyl methacrylate)/monomer systems are theoretically predictable from the moduli of the homopolymers involved. The above materials were generally ductile and the mechanical properties indicated a useful class of materials for clinical use.

Heterocyclic methacrylates for clinical applications. II. Room temperature polymerizing systems for potential clinical use.

A number of useful room temperature polymerizing resins were formulated, based on poly(ethyl methacrylate) powder and a range of low shrinkage heterocyclic methacrylate monomers. N,N-dimethyl-p-toluidine or p-tolyl diethanolamine were used as activating amines, but the latter material is less active and some care is necessary with respect to the source of the monomer. Isobornyl methacrylate is a useful diluent monomer to reduce the exotherm.

Heterocyclic methacrylates for clinical applications. III. Water absorption characteristics.

The water absorption and desorption behaviour of poly(isobornyl methacrylate) and poly(tetrahydropyran-2-ylmethyl methacrylate) obeyed diffusion laws on repeated absorption/desorption cycles. However, the polymers of 2,3-epoxypropyl, tetrahydrofurfuryl and tetrahydropyranyl methacrylates did not obey diffusion laws, did not equilibrate after 2 yr immersion in water and exhibited very high uptake values (30-90%). For 2,3-epoxypropyl methacrylate, the sample disintegrated. A clearly detailed structure of the heterocyclic ring is critical. The use of these monomers in room temperature polymerizing poly(ethyl methacrylate)/monomer systems generally reflected the behaviour of the related homopolymers.

Polymerization shrinkage of methacrylate esters.

The polymerization shrinkage of a range of poly(n-alkyl methacrylates) in the range C1 to C16, some of their isomers and the polymers of cyclic and heterocyclic methacrylates have been measured using densitometry. The percentage volume shrinkage decreases with the size of the substituent side group. This proved to reflect the fact that the change in molar volume on polymerizing a methacrylate ester is reasonably constant at 22 cc/mol irrespective of the geometry of the substituent group. However, the glass transition temperature of the polymer depends very critically on the geometry of the side group. Hence one method for the development of low shrinkage glassy polymers is to investigate methacrylate esters of large molar volume, but with side group geometry that results in a high glass transition temperature. Polymerization shrinkage can be used to determine the degree of conversion of a polymer, using the value of 22 cc/mol as the change in molar volume.

Refractive index and molar refraction of methacrylate monomers and polymers.

The refractive indices of a number of methacrylate monomers have been measured and corresponding molar refraction data calculated. Similar determinations were made on a number of methacrylate polymers. The molar refraction values determined were in excellent agreement with the values calculated from the published molar refraction values of the chemical groups involved. There was little difference between the molar refraction values of monomers and that of the repeat unit in the corresponding polymers, in marked contrast to the molar volumes. The ratio of refractive index to molar volume was reasonably consistent for all methacrylates studied (0.25-0.30 approximately).

The effect of two hydrophilic monomers on the water uptake of a heterocyclic methacrylate system.

The room temperature polymerising system poly(ethyl methacrylate) (PEM)/tetrahydrofurfuryl methcrylate (THFM) has been modified by replacing some of the THFM by hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPM), respectively. In both cases, the equilibrium uptake of the parent system is reduced substantially, in spite of the hydrophilic nature of these monomers. The effect is less with HPM. Corresponding to these decreases in uptake are substantial increases in the diffusion coefficients. This points to changes from a cluster-dominated process, to a more continuum-based process in the dual monomer systems. Addition of chicken serum albumin to these systems increases water uptake. At higher levels of HEMA addition, there is a substantial increase in polymerisation exotherm.

Nuclear magnetic imaging of an osmotic water uptake and delivery process.

The water absorption of NH4F-doped silicone cylinders was studied by spin-echo Fourier nuclear magnetic resonance imaging, in conjunction with gravimetric (mass uptake) and ionic concentration (release of NH4F) measurements. The addition of NH4F greatly increases the water uptake as the inclusions are surrounded by droplets of water when wetted by water diffusing in the polymer. These droplets then expand due to the osmotic pressure difference between the internal droplet and external solution; this expansion is opposed by an elastic restraining force. The rate of ingress into the polymer will depend on the relative chemical potential of water associated with the polymer and the droplet, as well as the diffusion coefficient. Later stages of the absorption process are dominated by the droplets. The dilution of the droplets (from water diffusing into the droplets) slowly reduces the chemical potential driving the process. Hence, the later stages occur without any notable concentration gradient but a slight chemical potential gradient. If the droplet expansion exceeds that which can be restrained by the material, failure around the droplet occurs resulting in the release of the salt and the solution within the droplet.

Fluoride ion release from two methacrylate polymer systems.

The release of fluoride ions from two room-temperature polymerising systems containing sodium and potassium fluoride, respectively, has been studied. The polymer systems comprised poly(ethyl methacrylate) powder (PEM), with tetrahydrofurfuryl methacrylate (THFM), and n-butyl methacrylate (nBM), respectively. The water uptake of these systems was drastically increased by the presence of fluorides, the increase being much higher with the PEM/THFM system. In both cases, uptake was a monotonic function of the molarity of the fluoride added. The uptake process was in general non-Fickian. However, for all systems, the fluoride release process was Fickian, and diffusion coefficients could be calculated. The amount of fluoride released, and the diffusion coefficients obtained, appeared unrelated to the extent of water uptake of the parent polymers.