Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant.

Although the immunological memory produced by BNT162b2 vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been well studied and established, further information using different racial cohorts is necessary to understand the overall immunological response to vaccination. We evaluated memory B and T cell responses to the severe acute respiratory syndrome coronavirus 2 spike protein before and after the third booster using a Japanese cohort. Although the Ab titer against the spike receptor-binding domain (RBD) decreased significantly 8 mo after the second vaccination, the number of memory B cells continued to increase, whereas the number of memory T cells decreased slowly. Memory B and T cells from unvaccinated infected patients showed similar kinetics. After the third vaccination, the Ab titer increased to the level of the second vaccination, and memory B cells increased at significantly higher levels before the booster, whereas memory T cells recovered close to the second vaccination levels. In memory T cells, the frequency of CXCR5+CXCR3+CCR6- circulating follicular Th1 was positively correlated with RBD-specific Ab-secreting B cells. For the response to variant RBDs, although 60-80% of memory B cells could bind to the omicron RBD, their avidity was low, whereas memory T cells show an equal response to the omicron spike. Thus, the persistent presence of memory B and T cells will quickly upregulate Ab production and T cell responses after omicron strain infection, which prevents severe illness and death due to coronavirus disease 2019.

Assessing anti-SARS-CoV-2 cellular immunity in 571 vaccines by using an IFN-γ release assay.

Memory T cell responses have been analyzed only in small cohorts of COVID-19 vaccines. Herein, we aimed to assess anti-SARS-CoV-2 cellular immunity in a large cohort using QuantiFERON assays, which are IFN-γ release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals receiving the viral spike (S) protein-expressing BNT162b2 mRNA vaccine. QuantiFERON assays revealed antigen-specific IFN-γ production in most individuals 8 weeks after the second dose. Simultaneous flow cytometric assays to detect T cells expressing activation-induced markers (AIMs) performed for 28 randomly selected individuals provided data correlating with the QuantiFERON data. Simultaneous IFN-γ enzyme-linked immunospot and AIM assays for another subset of 31 individuals, based on short-term peripheral blood mononuclear cell culture, also indicated a correlation between IFN-γ production and AIM positivity. These observations indicated the acquisition of T cell memory responses and supported the usability of IGRAs to assess cellular immunity. The QuantiFERON results were weakly correlated with serum IgG titers against the receptor-binding domain of the S protein and were associated with pre-vaccination infection and adverse reactions after the second dose. The present study revealed cellular immunity after COVID-19 vaccination, providing insights into the effects and adverse reactions of vaccination.

14- and 17-Membered Macrocycles Containing Amide, Amino, and Carbamate Groups in The Monocyclic Skeleton: An Accidental Byproduct Obtained from a Residue after Separation.

A 14-membered cyclic compound (3) containing amide, amino, and carbamate groups, which was serendipitously obtained in the oily residue after the separation of 4-benzyl-1,4,7,10-tetraazacyldododecane-2,6-dione (2a) and 4,16-dibenzyl-1,4,7,10,13,16,19,22-octaazacyclo-tetracosane-2,6,14,18-tetraone (2b), is reported. The structure of 3 is formally a CO2 insertion between positions 3 and 4 of the 12-membered ring in 2a. The CO2 insertion was confirmed in the synthesis of diethyl 2,2'-(benzylazanediyl)diacetate (1) by the reaction of benzylamine with ethyl bromoacetate using K2CO3 as the base. In addition, the selective synthesis of 3 and ethyl N-benzyl-N-((2-ethoxy-2-oxoethoxy)carbonyl)glycinate (5) and their kinetic behavior are reported. The reaction of 5 with triethylenetetramine afforded a 17-membered macrocycle (7), which was obtained in an 18% yield. Compounds 6 and 8 were prepared from 3 and 7 by introducing benzyl groups to improve their solubility in organic solvents. Titration experiments using 1H NMR showed that both 6 and 8 exhibit Li+ selectivity.

Regioselective Coordination toward Silver(I) Ions by Bis- and Tris(Tetra-Armed Cyclen)s via Differential Electron Density of Aromatic Side Arms.

Four types of bis- and tris(tetra-armed cyclen)s were prepared. 2MF is a bis(tetra-armed cyclen) with electron-rich side arms (three 4-methoxybenzyl groups) and electron-deficient side arms (three 3,5-difluorobenzyl groups), connected by a 4,4'-dimethyl-1,1'-biphenyl moiety. 3MFM is a tris(tetra-armed cyclen) with 4-methoxybenzyl and 3,5-difluorobenzyl groups introduced on both ends and the central cyclen, respectively. 4MFM is a V-shaped analogue of 3MFM. 3FMF is a tris(tetra-armed cyclen) where the aromatic side arms at both ends and the central cyclen of 3MFM are exchanged. The regioselective coordination of silver(I) ions by these ligands is reported. Initially, we added Ag+ ions to a compound (2MF) that consists of tetra-armed cyclen with 4-methoxybenzyl groups as an electron-donating substituent on the aromatic rings and 3,5-difluorobenzyl groups as an electron-withdrawing substituent. 1H NMR and 19F{1H} NMR spectroscopy exhibited that the cyclen with the 4-methoxybenzyl groups formed a complex with Ag+ ions first, followed by the cyclen with the 3,5-difluorobenzyl groups. Next, we employed a compound (3MFM) with three cyclen units, where the cyclen at each end was functionalized with three 4-methoxybenzyl groups, and the central cyclen was functionalized with two 3,5-difluorobenzyl groups. Upon adding Ag+ ions, we observed that the cyclen units at both ends formed complexes with Ag+ ions initially, followed by the central cyclen forming a complex with Ag+ ions. When we used 4MFM, which is a V-shaped compound, the Ag+-induced-1H NMR chemical shift changes are almost the same results as the 3MFM. Furthermore, we synthesized a compound (3FMF) by interchanging the substituents on the cyclen units at the ends and the center. Interestingly, the order of the complex formation was reversed in this compound. These results demonstrated that tuning the electron density on the aromatic side arms through substituents makes it possible to achieve regioselective coordination with Ag+ ions in bis- or tris(tetra-armed cyclen)s.

A Structure-Adaptive Ligand: The Conformation Changes to Fit with the Lengths and Angles of Tetravalent Bis-Paraquat Guests.

A flexible cylindrical cryptand (1b) with two m-phenylene-26-crown-8 ethers has been prepared, and its complexing properties with respect to tetravalent cationic bis-paraquat guests have been investigated. Diffusion-ordered spectroscopy nuclear magnetic resonance (NMR) and titration experiments using cold electrospray ionization mass spectrometry and 1H NMR revealed that 1b has versatile complexing properties with respect to tetravalent cationic guests used despite the guest molecules' length and shape.

Long-term influence of unintended pregnancy on psychological distress: a large sample retrospective cross-sectional study.

This study examined the associations between childbirth decisions in women with unintended pregnancies and long-term psychological distress. An online survey of women selected from a representative research panel was conducted in July 2021. Among participants who experienced an unintended pregnancy, the childbirth decision was categorized: (i) wanted birth, (ii) abortion, (iii) adoption, and (iv) unwanted birth. Participants who made childbirth decisions more than 1 year ago were included. ANCOVA was conducted with psychological distress (Kessler 6) as the dependent variable and education, marital status, years from the decision, age of the first pregnancy, economic situation at the unintended pregnancy, and the number of persons consulted at the unintended pregnancy as covariates. Logistic regression analysis was conducted for high distress (K6 ≥ 13) by adjusting the same covariates. A total of 47,401 respondents participated in the study. Women with an experience of unintended pregnancy experienced more than 1 year before the study were analyzed (n = 7162). Psychological distress was the lowest for wanted birth and increased for abortion, adoption, and unwanted birth. In the adjusted model, abortion was associated with lower distress scores than both adoption and unwanted birth. Compared to the wanted birth, adoption and unwanted birth showed significantly higher levels of distress (adjusted odds ratio [aOR] = 2.03 [95% CI 1.36-3.04], aOR = 1.64 [95% CI 1.04-2.58], respectively). Long-term effects on psychological distress differed according to the childbirth decisions in unintended pregnancy. Healthcare professionals should be aware of this hidden effect of unintended pregnancy experience on women's mental health.

Key strategies for managing nursing care under the COVID-19 pandemic: A multiple-case study of nursing directors.

AIM: We aim to identify measures implemented by hospital nursing directors early in the COVID-19 pandemic and enabling factors. BACKGROUND: Managerial factors affect nurses' physical and mental health and willingness to work, especially early in a pandemic. METHOD: We used multiple-case study of 15 hospitals, comparing management approaches by interviewing 28 nursing directors and their assistants from August to December 2020. RESULTS: Hospitals that accepted COVID-19 patients and hospitals that unexpectedly experienced clusters underwent a nursing provision system organization phase, followed by an adjustment phase to maintain nursing organization function. Two factors aided measure implementation: an emergency system and staff protection policies. CONCLUSION: Early epidemic management strategies apply across contexts. The hospital's basic attitude is key to effective implementation of the strategies. IMPLICATIONS FOR NURSING MANAGEMENT: The results suggest that hospitals, nursing directors and nurses can each prepare for future emerging infectious disease epidemics.

Cosmosen: Octa-Armed 24-Membered Cyclic Octaamine Synthesized from a Byproduct in the Preparation of 4-Benzyl-2,6-dioxocyclen.

The synthesis of an octa-armed 24-membered cyclic octaamine (1) is reported. When 4-benzyl-1,4,7,10-tetraazacyclododecane-2,6-dione (3a) was prepared by the reaction of diethylenetriamine with diethyl N-benzyliminodiacetate (2), a dimeric macrocycle (3b) was obtained as a byproduct in a 5% yield. An octa-armed 24-membered cyclic octaamine (1), named Cosmosen, was prepared via the reductive amination and reduction of 3b. The binding constants for the 1:1 and 2:1 (Ag+/1) complexation of 1 were estimated to be ca. 7.9 and 13.9, respectively, by titration experiments using UV-vis spectrometry in methanol and chloroform (v/v, 9:1) solutions at 298 K.

Argentivorous Molecules with Oxyethylene Chains in Side-Arms: Silver Ion-Induced Selectivity Changes toward Alkali Metal Ions.

Argentivorous molecules with mono, di, tri, tetra, and penta-oxyethylene chains in aromatic side-arms were prepared (L1-L5). Titration experiments using proton nuclear magnetic resonance and cold electrospray ionization (cold-spray ionization, CSI) mass spectrometry showed that silver ions were trapped in the cyclen moiety and the arranged oxyethylene chains of the side-arms when two equivalents of silver ions were added. The silver complexes formed by adding one equivalent of silver ion to L2-L5 bind alkali metal ions using the oxyethylene chains; alkali metal ion-induced CSI mass spectral changes of L2-L5 were measured in the absence and presence of silver ions to compare the binding properties of the ligand for Li+, Na+, and K+ ions. As a result, the intensity ratios of [L + H + M]2+/[L + H]+ in L1-L3 were almost zero or very low. L4 and L5, which have tetra(oxyethylene) and penta(oxyethylene) chains, respectively, bind a larger size of alkali metal ions. On the other hand, in the presence of silver ions, the ratio for [L + Ag + M]2+/[L + H]+ (M = Li, Na, K) in L2-L5 was increased. The highest [L + Ag + M]2+/[L + H]+ ratios for K+ were observed in L4 and L5, while selectivity for Na+ was observed in the case of L2 and L3. These results indicate that the increased binding ability and selectivity by L2-L5 are due to the arrangement of oxyethylene chains by the conformational change of the aromatic side-arms. The Ag+-induced carbon-13 nuclear magnetic resonance spectral changes suggested that the second and third oxyethylene units, close to the benzene, are involved in the coordination of the second metal ion.

Argentivorous Molecules with Chromophores in Side Arms: Silver Ion-Induced Turn On and Turn Off of Fluorescence.

The synthesis of argentivorous molecules (L1 and L2) having two chromophores (4-(anthracen-9-yl)benzyl or 4-(pyren-1-yl)benzyl groups) and two benzyl groups and the fluorescence properties of their silver complexes in a solution and the solid state are reported. A crystallographic approach for the Ag+ complexes with L1 and L2 revealed that the observed fluorescence changes stem from the excimer formation and extinction of fluorescent. Furthermore, binding stabilities of L1 and L2 toward Ag+ ions were estimated by the Ag+-induced UV-vis and PL spectral changes.

Mole-Ratio-Dependent Reversible Transformation between 2:2 and Cyclic 3:6 Silver(I) Complexes with an Argentivorous Molecule.

A tetra-armed cyclen (L) with two substituted 3,5-difluorobenzyl and two substituted pyridine-4-yl methyl groups at the 1,4- and 7,10-positions of the cyclen ring as side arms was synthesized. When L was reacted with 1 equiv of the silver(I), dimetallo[3.3]paracyclophane-like 2:2 cyclic dimer, [Ag2(L)2](PF6)2, was obtained. The reaction of L with 2 equiv of silver(I) gave a 3:6 cyclic trimer, [Ag6(L)3(CH3CN)3](OTf)6·3CH3CN. Furthermore, reversible complexation between the 2:2 cyclic dimer and 3:6 cyclic trimer was confirmed by 1H NMR and the CSI mass in the addition of silver(I) or the [2.2.2]cryptand.

Bis-Argentivorous Molecules Bridged by Phenyl and 4,4'-Biphenyl Groups: Structural and Dynamic Behavior of Silver Complexes.

Bis-argentivorous molecules (La and Lb), which have phenyl and 4,4'-biphenyl groups as linkers, have been prepared. The structures of Ag+ complexes with the new ligands (La and Lb) were investigated in solution and the solid state. The CSI-MS and 1H NMR titration of La and Lb with Ag+ show 1:1 and 1:2 complexes depending on the [Ag+]:[L] ratios. In the solid-state structures, single crystals of La and Lb with 2 equiv of Ag+ were prepared. X-ray crystallography of the silver(I) complexes with La and Lb showed that an intramolecular racemic structure (Δ(δδδδ)Λ(λλλλ) form) and a racemic mixture of Δ(δδδδ)Δ(δδδδ) and Λ(λλλλ)Λ(λλλλ) forms were formed, respectively. The dynamic 1H NMR studies suggest the following: (i) the activation entropies (ΔS⧧) of the side arm rotations in the Ag+ complex with La were all negative, indicating restricted rotation of the side arms due to their shortness, and (ii) the ΔS⧧ values of the Ag+ complexes with Lb were negative only when the side arms of both cyclens rotated simultaneously, and the ΔS⧧ values for the 1:1 and 1:2 complexes were positive when one cyclen side arm was rotated. These values of ΔS⧧ indicate that the biphenyl side arms between the two cyclens are not long enough to rotate the ring freely.

Pentacyclic Nano-Trefoil.

Tetra-armed cyclen (1) bearing two 4-(4'-pyridyl)benzyl and two 3,5-difluorobenzyl groups and its Ag+ complexes were prepared and structurally characterized. The complexes formed between 1 and Ag+ undergoes a reversible structural transformation between a 2:2 dimeric complex and a 3:5 pentacyclic trefoil complex with changes in the Ag+ /1 molar ratio. It was also revealed that the 3:5 trefoil complex could encapsulate benzene and [D6 ]benzene selectively in solid-state. The benzene-included structures are stabilized by C-H⋅⋅⋅F-C interactions between the benzene molecule and the ligand molecule.

Mechanistic insights into heavy metal ion sensing by NOS2-macrocyclic fluorosensors via the structure-function relationship: influences of fluorophores, solvents and anions.

To obtain a mechanistic understanding of the effects derived from fluorophores, solvents and anions on heavy metal sensing, two NOS2-macrocycle-based fluorosensors with different fluorophores (L1: 9-methylanthracene, L2: benzothiazolyl) were synthesised. In this regard, particular attention was given to monitoring the cation-ligand, cation-anion and cation-solvent interactions from the detailed complexation processes in both the solution and solid states while considering the structure-function relationship. L1 showed turn-on type silver(i) selectivity over other metal ions, including mercury(ii), in ethanol. According to the complexation results obtained by titration (UV-vis, fluorescence and NMR), cold-spray ionization mass spectrometry and X-ray crystallography, the observed silver(i) sensing by L1 is mainly due to its 1 : 1 complexation with silver(i) via the Ag-Ntert bond and the strong solvation of mercury(ii). Thus, the turn-on sensing for silver(i) can be explained by the CHEF effect, in which the coordination of silver(i) to the receptor unit effectively prevents PET quenching. As a dual-probe (UV-vis and fluorescence) chemosensor, L2 showed fluorescence turn-off type selectivity for both silver(i) and mercury(ii) in ethanol. In acetonitrile, L2 showed improved fluorescence turn-off type selectivity for mercury(ii) with ClO4- and NO3-; however, no such responses were observed with other anions, such as Cl-, Br-, I-, SCN-, OAc- and SO42-. Together with the complexation results by titration, the crystal structures of an endocyclic mercury(ii) perchlorate complex and an exocyclic mercury(ii) iodide complex revealed that the anion-controlled mercury(ii) sensing by L2 arises from the endo- and exo-coordination modes depending on the anion coordinating ability, which induces either metal-receptor/fluorophore binding (Hg-Ntert and Hg-Nfl) or no binding. Taken collectively, the photophysical, thermodynamic and structural results of the complexations herein suggest that the sensing properties of heavy metal ions by macrocycle-based fluorosensors are very sensitive not only to the cation-receptor and cation-fluorophore interactions but also to the cation-anion (endo/exo-coordination modes) and/or cation-solvent interactions.

Influence of the Molar Ratio and Solvent on the Coordination Modes of 1,7-Dibenzyl-4,10-bis(pyridin-4-ylmethyl)cyclen.

The synthesis of a tetra-armed cyclen (L) with two benzyl groups at the 1- and 7-positions and two pyridin-4-ylmethyl groups at the 4- and 10-positions as side arms and the solvent- and/or molar-ratio-dependent coordination modes in the formation of silver(I) complexes are reported. 1H NMR and cold-spray-ionization mass spectrometry studies suggest that a silver(I) complex with L gives different species depending on the molar ratio of silver ions used as the reactant. Furthermore, the conformation of cyclen in the one-dimensional (1D) coordination polymers, obtained using 2 equiv of silver(I), changes depending on the presence or absence of acetonitrile. When L was reacted with 1 and 2 equiv of silver(I) triflate in a mixed solvent system (CH2Cl2/CH3OH/CH3CN), a dimetallo[3.3]paracyclophane-like discrete cyclic dimer, [Ag2L2](OTf)2 (1), and a 1D coordination polymer, [Ag2L(OTf)2(CH3CN)]n (2), respectively, were obtained as single crystals. In the absence of acetonitrile, a zigzag 1D coordination polymer, {[Ag2L(OTf)]OTf·3CH2Cl2}n (3), was obtained when 2 equiv of silver(I) was used. Molar-ratio-dependent structural changes were not observed when L was reacted with AgBF4 or AgPF6 in the CH2Cl2/CH3OH/CH3CN mixed-solvent system. The solvent effect on the coordination modes can be explained by the coordination ability of the solvents toward the metal cation affecting the conformation of the cyclen.

Argentivorous Molecules Exhibiting Highly Selective Silver(I) Chiral Enhancement.

We report the synthesis of chiral tetra-armed cyclens, having an asymmetric center at one side-arm, that show selective chiral enhancement with silver(I). When the chiral ligand forms a silver(I) complex, the side-arms cover the silver(I) incorporated into the cyclen. The asymmetric center controls the conformation of the side-arms in one direction, increasing the molar ellipticity of the CD spectrum. Chiral cyclens substituted with biphenyl groups exhibit large molar ellipticity values with strong exciton coupling effects.

1H NMR Study of a Chiral Argentivorous Molecule/Ag+ Complex: Assignment of Proton Signals of Four Aromatic Rings with Slightly Different Environments.

The proton signals at the 2'- and 6'-positions of the aromatic side arms of a silver(I) complex with a chiral tetra-armed cyclen ((S)-L2) are assigned by comparison with 1H NMR spectra and X-ray structure of Ag+ complexes with three analogues of (S)-L2: (S)-L23D having one benzyl group and three deuterium-substituted benzyl groups, (S)-L22D having two benzyl groups and two deuterium-substituted benzyl groups, and (S)-L2F having three benzyl groups and one 4'-fluorobenzyl group. An interaction factor is defined by using the X-ray structures. The chemical shift values of the proton signals in the aromatic side arms can be explained by using the interaction factors that are defined by the dihedral angles, the angles between two mean planes, and the CH···π distances from the X-ray data of the (S)-L2/Ag+ complex.

Frontline nurse managers' visions for their units: A qualitative study.

AIMS: To elucidate frontline nurse managers' visions of their units. BACKGROUND: Managers have the opportunity to imagine and share their visions for effective unit management. METHODS: Semi-structured interviews were conducted with 12 frontline nurse managers working at inpatient units in two hospitals between 2016 and 2017. Data were qualitatively analysed using an inductive approach, focusing on participants' intents. RESULTS: Although participants showed four types of difficulties in verbalizing visions, five categories and 18 subcategories were extracted through analysis of their descriptions about actual cases reflecting their visions. The categories were (a) provide excellent care to ensure patient recovery based on reliable knowledge and skills, (b) make efforts to broaden patients' futures, (c) create a climate for pursuing better practice, (d) all staff continuously pursue professional development and (e) provide nursing care that responds to external changes. All categories were common to all participants' images of the future and linked together to form each manager's vision. CONCLUSION: Frontline managers experienced difficulty in articulating their visions. However, through episodes, they represented images of visions. The managers' visions comprised five categories reflecting various perspectives. IMPLICATIONS FOR NURSING MANAGEMENT: Using a conceptualized vision framework, and identifying difficulties in verbalizing their images, can help managers articulate their visions.

Pillar[5]-bis-thiacrown: An Adaptive Tricyclic Host Selectively Recognizing an Organic Guest by Dimetalation.

Some biological receptors change their shapes and rigidity by metalation to recognize substrates precisely via adaptive guest binding process. Herein we present a semi-flexible tricyclic host molecule whose conformation is rigidified by dimetalation to uptake organic guests selectively. Considering two metal binding sites and an empty space between them, pillar[5]-bis-thiacrown (L) was synthesized. The tricyclic host L forms a disilver(I) complex [Ag2 L(NO3 )2 ], with an Ag⋅⋅⋅Ag separation of 9.976 Å. Binding studies based on 1 H NMR including 2D NOESY and DOSY experiments towards α,ω-dicyanoalkanes [CN(CH2 )n CN, n=2-6, shortly C2-C6] demonstrated that the dimetalated L, Ag2 L preferentially recognizes C2 over other guests than that of free L. Furthermore, the dimetalated the host only uptakes C2 in the presence of other guests. Crystal structures support the idea that the space between two silver(I) centers plays a decisive role on the selective guest binding forming an Ag-C2-Ag@L arrangement via the length-selective recognition. This work demonstrates the chemical example of the adaptive guest binding and presents a new perspective on the metallosupramolecules of pillararenes.

Conventional and Mechanochemical Syntheses of Copper(I) Iodide Luminescent MOF with Bis(amidoquinoline) and Its Application for the Detection of Amino Acid in Aqueous Solution.

Formation of a copper(I) iodide cluster based luminescent metal-organic frameworks (LMOFs) and its utilization for the detection of cysteine (Cys) in aqueous solution are reported. The reaction of bis(amidoquinoline) ligand (L) with copper(I) iodide afforded an LMOF {[(Cu2I2)L2]·2DMSO} n (1) with a 44-sql topology linked by Cu2I2 clusters as a thermodynamic product. Time- and temperature-dependent PXRD experiments confirmed that the entire formation process for 1 is kinetically and thermodynamically controlled. Interestingly, LMOF 1 was also obtained under the mechanochemical condition. Moreover, LMOF 1 dispersed in water shows a selective quenching for Cys over other amino acids due to the strong affinity of Cys to copper(I) iodide. On the basis of the NMR data of L isolated from the decomposition of 1, the decomposition-displacement mechanism was proposed for the sensing of Cys. This result might be utilized for the practical detection of Cys because the sensing material can be prepared simply, and the sensing process is performed in aqueous media.