Methyl 2-{6-[(1-meth­oxy-1-oxopropan-2-yl)amino­carbon­yl]pyridine-2-carboxamido}­propano­ate

In the title compound, C15H19N3O6, the amide planes are inclined at dihedral angles of 0.8 (6) and 12.1 (3)° with respect to the central pyridine ring. The mean planes of the corresponding methyl acetate groups form dihedral angles of 41.76 (13) and 86.48 (15)°, respectively with the mean plane of pyridine ring. A pair of weak intra­molecular N—H⋯N hydrogen bonds generate an S(5)S(5) ring motif in the mol­ecule. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into [001] chains. The chains are cross-linked by C—H⋯O hydrogen bonds into layers lying parallel to bc plane. The crystal packing also features a C—H⋯π inter­action

Neutrophil functions in late preterm neonates with respiratory distress syndrome

Background: Studies that have addressed the effects of respiratory distress syndrome (RDS) on neutrophil function suggested that neutrophil functions other than the generation of the respiratory burst are not impaired. Yet, results have been confusing and in some cases contradictory.Objectives: The aim of this cross-sectional controlled study is to assess neutrophil number and function in late preterm neonates with RDS.Methods: Thirty patients underwent clinical and laboratory evaluation including complete blood counts and tests of neutrophil functions (CD11b, CD62L and Dihydrorhodamine 123 by flowcytometry) in comparison to 15 healthy term controls. RDS was assessed clinically and radiologically (chest x-ray).Results: Fifty percent of patients (12 females and 18 males) had grade II respiratory distress followed by grade III then grade I. DHR, CD 11b and CD62L results were lower among the patients group (mean ± SD: 62.1± 12.23, 63.22 ± 11.41, 15.03 ± 8.7 respectively). There were no significant correlations between neutrophils count, DHR, CD11b and CD62L. Only CD11b was significantly lower with higher grades of RDS.Conclusion: Neonates with RDS show variable affection of neutrophil functions. Further studies are recommended to elucidate the exact mechanisms by which RDS can affect neutrophil functions and whether these effects are associated with increased incidence of infections.Keywords: Neutrophils, function, respiratory distress syndrome, late preterm, innate immunity, infections, adhesion molecule

Ethyl 2-amino-4-(4-fluoro­phen­yl)-6-meth­oxy-4H-benzo[h]chromene-3-carboxyl­ate

In the title compound, C23H20FNO4, the fluoro-substituted benzene ring is approximately perpendicular to the mean plane of the 4H-benzo[h]chromene ring system [maximum deviation = 0.264 (1) Å], with a dihedral angle of 83.79 (6)°. The pyran ring adopts a flattened boat conformation. The meth­oxy group is slightly twisted from the attached benzene ring of the 4H-benzo[h]chromene moiety [C—O—C—C = −2.1 (2)°]. An intra­molecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, mol­ecules are linked by N—H⋯O and N—H⋯F hydrogen bonds into a layer parallel to the bc plane. The crystal packing also features C—H⋯π inter­actions

Heterociklički derivati 3-(4-bromfenil) azo-5-fenil-2(3H)-furanona: Djelovanje na virus ptičje gripe (H5N1)

3-[2-(4-Bromphenyl)hydrazono]-5-phenyl-furan-2(3H)-one (1) was used for preparation of some novel pyrazole, pyridazinone, oxadiazole, triazole, thiazolidine and thioxo-pyrimidine derivatives. Some of the prepared products were tested for anti-avian influenza virus activity and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/20 % (H5N1)] by determination of both EC50 and LD50 and confirmed by plaque reduction assay on MDCK cells. Compounds 3-[2-(4-bromophenyl)hydrazono]-5-phenylfuran-2(3H)-one 1, 1-(4-bromophenyl)-N-hydroxy-5-phenyl-1H-pyrazole-3-carboxamide 5 and 1-(4-bromophenyl)-N-{2,3-dihydro-4-hydroxy-3-phenyl-6-oxo-2-thioxopyrimidin-1(6H)-yl}-5-phenyl-1H-pyrazole-3-carboxamide (12a) showed the highest effects. Detailed synthesis, spectroscopic data, and antiviral activity of the synthesized compounds are reported.3-[2-(4-Bromfenil)hidrazono]-5-fenil-furan-2(3H)-on (1) upotrjebljen je za pripravu novih derivata pirazola, piridazinona, oksadiazola, triazola, tiazolidina i tioksopirimidina. Neki od sintetiziranih spojeva imaju virustatski učinak na virus ptičje gripe H5N1. Farmakološki aktivnim spojevima određeni su EC50 i LD50 i dobiven je pozitivni test redukcije plaka na MDCK staničnoj liniji. Najjači učinak pokazali su 3-[2-(4-bromfenil)hidrazono]-5-fenilfuran-2(3H)-on (1), 1-(4-bromfenil)-N-hidroksi-5-fenil-1H-pirazol-3-karboksamid (5) i 1-(4-bromfenil)-N-{2,3-dihidro-4-hidroksi-3-fenil-6-okso-2-tioksopirimidin-1(6H)-il}-5-fenil-1H-pirazol-3-karboksamid (12a). Detaljno su opisani priprava, spektroskopski podaci i antivirusno djelovanje sintetiziranih spojeva

Methyl 2-({6-[(1-meth­oxy-2-methyl-1-oxopropan-2-yl)carbamo­yl]pyridin-2-yl}formamido)-2-methyl­propano­ate

In the title compound, C17H23N3O6, the two meth­oxy­carbonyl C—O—C=O planes are inclined at dihedral angles of 5.3 (4) and 83.9 (4)° with respect to the central pyridine ring. An intra­molecular N—H⋯O hydrogen bond generates an S(5) ring motif. In the crystal, mol­ecules are linked into a chain along the c axis via C—H⋯O hydrogen bonds

Serotonin 5-HT4 receptor boosts functional maturation of dendritic spines via RhoA-dependent control of F-actin

Activity-dependent remodeling of excitatory connections underpins memory formation in the brain. Serotonin receptors are known to contribute to such remodeling, yet the underlying molecular machinery remains poorly understood. Here, we employ high-resolution time-lapse FRET imaging in neuroblastoma cells and neuronal dendrites to establish that activation of serotonin receptor 5-HT4 (5-HT4R) rapidly triggers spatially-restricted RhoA activity and G13-mediated phosphorylation of cofilin, thus locally boosting the filamentous actin fraction. In neuroblastoma cells, this leads to cell rounding and neurite retraction. In hippocampal neurons in situ, 5-HT4R-mediated RhoA activation triggers maturation of dendritic spines. This is paralleled by RhoA-dependent, transient alterations in cell excitability, as reflected by increased spontaneous synaptic activity, apparent shunting of evoked synaptic responses, and enhanced long-term potentiation of excitatory transmission. The 5-HT4R/G13/RhoA signaling thus emerges as a previously unrecognized molecular pathway underpinning use-dependent functional remodeling of excitatory synaptic connections

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries