Epidermal anti-Inflammatory properties of 5,11,14 20:3: Effects on mouse ear edema, PGE(2 )levels in cultured keratinocytes, and PPAR activation

BACKGROUND: 5,11,14 20:3 is similar to 20:4n-6 but lacks the internal Δ8 double bond essential for prostaglandin and eicosanoid synthesis. When previously fed to laboratory animals as a gymnosperm seed oil component it has shown anti-inflammatory properties. RESULTS: Herein, topically applied Podocarpus nagi methyl esters (containing 26% 5,11,14 20:3) were incorporated into mouse ear phospholipids, reduced 20:4n-6, and reduced 20:4n-6- and TPA-induced mouse ear edema. Purified 5,11,14 20:3 was taken up by cultured human skin keratinocytes, reduced 20:4n-6, and reduced PGE(2 )levels dramatically. Purified 5,11,14 20:3 did not affect PPARα, PPARγ, or PPARδ transactivation. CONCLUSIONS: Topical application of 5,11,14 20:3 to skin surfaces can thus reduce inflammatory processes, most likely by displacing 20:4n-6 from phospholipid pools and reducing downstream inflammatory products derived from 20:4n-6 such as PGE(2 )and leukotrienes. It could have potential use in treating clinical skin disorders resulting from overproduction of 20:4n-6-derived eicosanoid products

Unusual suppression of the superconducting energy gap and critical temperature in atomically thin NbSe2

It is well known that superconductivity in thin films is generally suppressed with decreasing thickness. This suppression is normally governed by either disorder-induced localization of Cooper pairs, weakening of Coulomb screening, or generation and unbinding of vortex-antivortex pairs as described by the Berezinskii-Kosterlitz-Thouless (BKT) theory. Defying general expectations, few-layer NbSe2 - an archetypal example of ultrathin superconductors - has been found to remain superconducting down to monolayer thickness. Here we report measurements of both the superconducting energy gap and critical temperature in high-quality monocrystals of few-layer NbSe2, using planar-junction tunneling spectroscopy and lateral transport. We observe a fully developed gap that rapidly reduces for devices with the number of layers N < 5, as does their ctitical temperature. We show that the observed reduction cannot be explained by disorder, and the BKT mechanism is also excluded by measuring its transition temperature that for all N remains very close to Tc. We attribute the observed behavior to changes in the electronic band structure predicted for mono- and bi- layer NbSe2 combined with inevitable suppression of the Cooper pair density at the superconductor-vacuum interface. Our experimental results for N > 2 are in good agreement with the dependences of the gap and Tc expected in the latter case while the effect of band-structure reconstruction is evidenced by a stronger suppression of the gap and the disappearance of its anisotropy for N = 2. The spatial scale involved in the surface suppression of the density of states is only a few angstroms but cannot be ignored for atomically thin superconductors.Comment: 21 pages, including supporting informatio

A Conserved Ethylene Biosynthesis Enzyme Leads to Andromonoecy in Two Cucumis Species

Andromonoecy is a widespread sexual system in angiosperms, characterized by plants carrying both male and bisexual flowers. Monoecy is characterized by the presence of both male and female flowers on the same plant. In cucumber, these sexual forms are controlled by the identity of the alleles at the M locus. In melon, we recently showed that the transition from monoecy to andromonoecy result from a mutation in 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene, CmACS-7. To isolate the andromonoecy gene in cucumber we used a candidate gene approach in combination with genetical and biochemical analysis. We demonstrated co-segregation of CsACS2, a close homolog of CmACS-7, with the M locus. Sequence analysis of CsACS2 in cucumber accessions identified four CsACS2 isoforms, three in andromonoecious and one in monoecious lines. To determine whether the andromonoecious phenotype is due to a loss of ACS enzymatic activity, we expressed the four isoforms in Escherichia coli and assayed their activity in vitro. Like in melon, the isoforms from the andromonoecious lines showed reduced to no enzymatic activity and the isoform from the monoecious line was active. Consistent with this, the mutations leading andromonoecy were clustered in the active site of the enzyme. Based on this, we concluded that active CsACS2 enzyme leads to the development of female flowers in monoecious lines, whereas a reduction of enzymatic activity yields hermaphrodite flowers. Consistent with this, CsACS2, like CmACS-7 in melon, is expressed specifically in carpel primordia of buds determined to develop carpels. Following ACS expression, inter-organ communication is likely responsible for the inhibition of stamina development. In both melon and cucumber, flower unisexuality seems to be the ancestral situation, as the majority of Cucumis species are monoecious. Thus, the ancestor gene of CmACS-7/CsACS2 likely have controlled the stamen development before speciation of Cucumis sativus (cucumber) and Cucumis melo (melon) that have diverged over 40 My ago. The isolation of the genes for andromonoecy in Cucumis species provides a molecular basis for understanding how sexual systems arise and are maintained within and between species

Perfluoroalkyl acids (PFAAs) in children’s serum and contribution from PFAA-contaminated drinking water

We investigated associations between serum perfluoroalkyl acid (PFAA) concentrations in children aged 4, 8, and 12 years (sampled in 2008–2015; n = 57, 55, and 119, respectively) and exposure via placental transfer, breastfeeding, and ingestion of PFAA-contaminated drinking water. Sampling took place in Uppsala County, Sweden, where the drinking water has been historically contaminated with perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), perfluoroheptanoate (PFHpA), and perfluorooctanoate (PFOA). PFOS showed the highest median concentrations in serum (3.8–5.3 ng g–1 serum), followed by PFHxS (1.6–5.0 ng g–1 serum), PFOA (2.0–2.5 ng g–1 serum), and perfluorononanoate (PFNA) (0.59–0.69 ng g–1 serum) in children. Including all children, serum PFOA, PFHxS, and PFOS concentrations in children increased 10, 10, and 1.3% (adjusted mean), respectively, per unit (ng g–1 serum) of increase in the maternal serum level (at delivery), the associations being strongest for 4 year-old children. PFHxS and PFOS significantly increased 3.9 and 3.8%, respectively, per month of nursing, with the highest increase for 4 year-olds. PFOA, PFBS, PFHxS, and PFOS increased 1.2, 207, 7.4, and 0.93%, respectively, per month of cumulative drinking water exposure. Early life exposure to PFOA, PFHxS, and PFOS is an important determinant of serum concentrations in children, with the strongest influence on younger ages. Drinking water with low to moderate PFBS, PFHxS, PFOS, and PFOA contamination is an important source of exposure for children with background exposure from other sources

Analytical modeling and vibration analysis of partially cracked rectangular plates with different boundary conditions and loading

This study proposes an analytical model for vibrations in a cracked rectangular plate as one of the results from a program of research on vibration based damage detection in aircraft panel structures. This particular work considers an isotropic plate, typically made of aluminum, and containing a crack in the form of a continuous line with its center located at the center of the plate and parallel to one edge of the plate. The plate is subjected to a point load on its surface for three different possible boundary conditions, and one examined in detail. Galerkin's method is applied to reformulate the governing equation of the cracked plate into time dependent modal coordinates. Nonlinearity is introduced by appropriate formulations introduced by applying Berger's method. An approximate solution technique—the method of multiple scales—is applied to solve the nonlinear equation of the cracked plate. The results are presented in terms of natural frequency versus crack length and plate thickness, and the nonlinear amplitude response of the plate is calculated for one set of boundary conditions and three different load locations, over a practical range of external excitation frequencies

Methods for think-aloud interviews in health-related resource-use research:the PECUNIA RUM instrument

The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent’s perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A ‘before the interview’ (including translation, recruitment, training), Part B ‘during the interview’ (including setting, opening, completing the instrument, open-ended questions, closing), and part C ‘after the interview’ (including transcription and data analysis, trustworthiness). This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.</p

Clinical relevance and implementation into daily practice of pharmacist-prescribed medication for the management of minor ailments

Background: Autonomous pharmacist prescribing was legally introduced in Switzerland in 2019 with the reclassification from prescription medication to pharmacist prescribing of 105 medications for sixteen indications. Its aim was to limit medical consultations and healthcare costs.Objectives: To evaluate the clinical relevance of the pharmacy prescribing medications compared to the over-the-counter medications (OTCs) and to evaluate its implementation into daily practice.Methods: A comparison was undertaken by clinical pharmacists to evaluate chemical and galenical equivalences between pharmacy prescribing medications and OTCs using compendium. ch and pharmavista. ch. Then, a scoping review was carried out in October 2021 to determine clinical relevance according to clinical guidelines’ recommendations. Clinical relevance was completed by determining if pharmacy prescribing medications were part of a homogeneous therapeutic class (no differences in efficacy and safety considered in clinical guidelines, but rather inter-molecular differences) that included an OTC medication. To identify the most clinically relevant pharmacy prescribing medications, first-line treatments were considered. The implementation into daily practice in Swiss community pharmacies was evaluated through an online questionnaire distributed via e-mail from the national pharmacists’ association and LinkedIn®. It included 15 questions divided in: pharmacy demographics, experience on pharmacy prescribing, use of prescribing medications and opinion about the them.Results: Of the 105 pharmacy prescribing medications, 20 (19.0%) were first-line treatments without OTC equivalences. Six of them were OTCs reclassified for safety reasons. Ten medications (9.5%) showed a negative clinical relevance (they were not first-line therapeutic options to support pharmacist when managing patients or considered as to be avoided) compared to the OTCs available. For the questionnaire, 283 pharmacists from the German (40.3%), French (37.1%) and Italian-speaking regions (16.9%) answered. In the previous 6 months, 41.7% pharmacies had delivered 10–50 medications and 30.0% between 1 and 10 medications. In situations where patients could be equally treated with a pharmacy prescribing medication or OTC (with an identical OTC, similar OTC or an OTC for the same therapeutic group): 75.6%, 74.9% and 84.8% of pharmacists, respectively, would have chosen OTCs because it required less documentation and it did not require patients’ payment for the service. In addition, pharmacists’ lack of training was also mentioned as barrier for providing the service.Conclusion: Most pharmacist prescribing medications do not present clinical advantages compared to OTCs. In addition, other barriers for implementation were also pharmacists’ training and patient medications costs

Critical Examination of the "Field-Theoretical Approach" to the Neutron-Antineutron Oscillations in Nuclei

We demonstrate that so called "infrared divergences" which have been discussed in some publications during several years, do not appear within the correct treatment of analytical properties of the transition amplitudes, in particular, of the second order pole structure of the amplitudes describing the $n - \bar n$ transition in nuclei. Explicit calculation with the help of the Feynman diagram technique shows that the neutron-antineutron oscillations are strongly suppressed in the deuteron, as well as in heavier nuclei, in comparison with the oscillations in vacuum. General advantages and some difficulties of the field theoretical methods applied in nuclear theory are reminded for the particular example of the parity violating $np\to d\gamma$ capture amplitude.Comment: 15 pages, 4 figures; prepared for Eur.Phys.J.

Perfluoroalkyl Acids (PFAAs) in Serum from 2-4-Month-Old Infants: Influence of Maternal Serum Concentration, Gestational Age, Breast-Feeding, and Contaminated Drinking Water

Little is known about factors influencing infant perfluorinated alkyl acid (PFAA) concentrations. Associations between serum PFAA concentrations in 2-4-month-old infants (n = 101) and determinants were investigated by multiple linear regression and general linear model analysis. In exclusively breastfed infants, maternal serum PFAA concentrations 3 weeks after delivery explained 13% (perfluoroundecanoic acid, PFUnDA) to 73% (perfluorohexanesulfonate, PFHxS) of infant PFAA concentration variation. Median infant/maternal ratios decreased with increasing PFAA carbon chain length from 2.8 for perfluoroheptanoic acid and perfluorooctanoic acid (PFOA) to 0.53 for PFUnDA and from 1.2 to 0.69 for PFHxS and perfluorooctanesulfonate (PFOS). Infant PFOA, perfluorononanoic acid (PFNA), and PFOS levels increased 0.7-1.2% per day of gestational age. Bottle-fed infants had mean concentrations of PFAAs 2 times lower than and a mean percentage of branched (%br) PFOS isomers 1.3 times higher than those of exclusively breast-fed infants. PFOA, PFNA, and PFHxS levels increased 8-11% per week of exclusive breast-feeding. Infants living in an area receiving PFAA-contaminated drinking water had 3-fold higher mean perfluorobutanesulfonate (PFBS) and PFHxS concentrations and higher mean %br PFHxS. Prenatal PFAA exposure and postnatal PFAA exposure significantly contribute to infant PFAA serum concentrations, depending on PFAA carbon chain length. Moderately PFBS- and PFHxS-contaminated drinking water is an important indirect exposure source

First histological observations on the incorporation of a novel nanocrystalline hydroxyapatite paste OSTIM(® )in human cancellous bone

BACKGROUND: A commercially available nanocrystalline hydroxyapatite paste Ostim(® )has been reported in few recent studies to surpass other synthetic bone substitutes with respect to the observed clinical results. However, the integration of this implantable material has been histologically evaluated only in animal experimental models up to now. This study aimed to evaluate the tissue incorporation of Ostim(® )in human cancellous bone after reconstructive bone surgery for trauma. METHODS: Biopsy specimens from 6 adult patients with a total of 7 tibial, calcaneal or distal radial fractures were obtained at the time of osteosynthesis removal. The median interval from initial operation to tissue sampling was 13 (range 3–15) months. Samples were stained with Masson-Goldner, von Kossa, and toluidine blue. Osteoid volume, trabecular width and bone volume, and cortical porosity were analyzed. Samples were immunolabeled with antibodies against CD68, CD56 and human prolyl 4-hydroxylase to detect macrophages, osteoblasts, and fibroblasts, respectively. TRAP stainings were used to identify osteoclasts. RESULTS: Histomorphometric data indicated good regeneration with normal bone turnover: mean osteoid volume was 1.93% of the trabecular bone mass, trabecular bone volume – 28.4%, trabecular width – 225.12 μm, and porosity index – 2.6%. Cortical and spongious bone tissue were well structured. Neither inflammatory reaction, nor osteofibrosis or osteonecrosis were observed. The implanted material was widely absorbed. CONCLUSION: The studied nanocrystalline hydroxyapatite paste showed good tissue incorporation. It is highly biocompatible and appears to be a suitable bone substitute for juxtaarticular comminuted fractures in combination with a stable screw-plate osteosynthesis