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Background: To examine visual outcome and vision related quality of life after Implantable Collamer Lens for Moderate to High Myopia and Myopic Astigmatism. Material and methods: A hospital-based prospective, interventional, observational study has been carried out to evaluate functional outcomes and patient satisfaction following phakic ICL implantation for the treatment of myopia and myopic astigmatism. In this study, we included 44 eyes of 26 patients, 15 females (58%) and 11 males (42%), mean age 24.56 ± 4.98 years (range: 18-35) with preoperative myopia (mean ± standard deviation [SD] refraction spherical equivalent, -11.485 ± 4.78 D). To investigate the effects of ICL implantation, we had compared between two groups: one group before surgery and another group one month after surgery. Measurements including uncorrected distance visual acuity (UCVA), corrected distance visual acuity (CDVA), spherical equivalent (SE) of manifest refraction, and corneal topography were obtained for all participants. The Quality-of-Life Impact of Refractive Correction (QIRC) questionnaire was administered to compare VRQOL between before and after ICL implantation. Results: The postoperative mean UCVA demonstrated a significant statistical improvement (p

Background: Palliative care is an essential element of universal healthcare, yet not all people who need palliative care are able to receive it. One of the barriers to ensuring access for people who require palliative care is the identification of those eligible. Aim: This study evaluated healthcare workers’ ability to identify patients who are eligible for palliative care based on their training or experience in palliative care. Setting: The setting for the study comprised the Heideveld Emergency Centre and Heideveld Community Day Centre in the Cape Metro, Cape Town, South Africa. Methods: This study made use of a cross-sectional survey of healthcare workers. Results: Of the 55 participants in this study, most were able to correctly identify patients with cancer and chronic kidney disease as needing palliative care, but less accurate with other organ failure categories, trauma indications, or functional assessment of the patient. Participants who reported previous awareness training reported improved knowledge on the indications for a palliative care approach compared to no prior training. Conclusion: Our cohort was too small to analyse the results statistically. From what was analysed, the ability of healthcare workers to identify a person in need of palliative care could be better; more work is needed on our awareness training and basic training courses to improve this vital step. Contribution: This research highlights the fact that existing training for palliative care needs to be more applicable to the setting and that training of staff with existing courses does make a difference in knowledge.

Summary: Here we present a protocol to engineer apical-out airway organoids (AOAOs) directly from human airway basal stem cells (hABSCs) using suspension culture of hABSC aggregates on a cell-repellent surface. We describe steps to produce spherical AOAOs with homogenous presentation of exterior-facing motile cilia and of tunable sizes. We then detail procedures to analyze AOAO cellular composition via wholemount staining and assess cilia motility via 3D AOAO rotation upon Matrigel embedding. The protocol offers an effective model for investigating human airway pathophysiology.For complete details on the use and execution of this protocol, please refer to Wijesekara et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

New classes of antibiotics are urgently needed in the fight against multidrug-resistant bacteria. Drug repurposing has emerged as an alternative approach to accelerate antimicrobial research and development. In this study, we screened a library of sphingosine-1-phosphate receptor (S1PR) modulators against Staphylococcus aureus and identified five active compounds. Among them, etrasimod (APD334), an investigational drug for the treatment of ulcerative colitis, displayed the best inhibitory activity against S. aureus when growing as free-floating planktonic cells and within biofilms. In follow-up studies, etrasimod showed bactericidal activity and drastic reduction of viable bacteria within 1 h of exposure. It also displayed a potent activity against other Gram-positive bacteria, including penicillin- and methicillin-resistant S. aureus strains, S. epidermidis, and Enterococcus faecalis, with a minimum inhibitory concentration (MIC) ranging from 5 to 10 μM (2.3–4.6 μg/mL). However, no inhibition of viability was observed against Gram-negative bacteria Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa, showing that etrasimod preferably acts against Gram-positive bacteria. On the other hand, etrasimod was shown to inhibit quorum sensing (QS) signaling in Chromobacterium violaceum, suggesting that it may block the biofilm formation by targeting QS in certain Gram-negative bacteria. Furthermore, etrasimod displayed a synergistic effect with gentamicin against S. aureus, thus showing potential to be used in antibiotic combination therapy. Finally, no in vitro toxicity toward mammalian cells was observed. In conclusion, our study reports for the first time the potential of etrasimod as a repurposed antibacterial compound against Gram-positive bacteria.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

The change of the shell structure in atomic nuclei, so-called “nuclear shell evolution”, occurs due to changes of major configurations through particle-hole excitations inside one nucleus, as well as due to variation of the number of constituent protons or neutrons. We have investigated how the shell evolution affects Gamow-Teller (GT) transitions that dominate the β decay in the region below 132Sn using the newly obtained experimental data on a long-lived isomer in 127Ag. The T1/2=67.5(9) ms isomer has been identified with a spin and parity of (27/2+) at an excitation energy of 1942−20+14 keV, and found to decay via an internal transition of an E3 character, which competes with the dominant β-decay branches towards the high-spin states in 127Cd. The underlying mechanism of a strong GT transition from the 127Ag isomer is discussed in terms of configuration-dependent optimization of the effective single-particle energies in the framework of a shell-model approach.

Disrupting bacterial quorum sensing (QS) signaling is a promising strategy to combat pathogenic biofilms without the development of antibiotic resistance. Here, we report that food-associated bacteria can interfere with the biofilm formation of a Gram-negative pathogenic bacterium by targeting its AHL (acyl-homoserine lactone) QS system. This was demonstrated by screening metabolic end-products of different lactobacilli and propionibacteria using Gram-negative and biofilm-forming Chromobacterium violaceum as the QS reporter and our anti-QS microscale screening platform with necessary modifications. The method was optimized in terms of the inoculation technique and the concentrations of D-glucose and L-tryptophan, two key factors controlling the synthesis of violacein, a purple pigment indicating the activation of the QS system in C. violaceum. These improvements resulted in ca. 16-times higher violacein yields and enabled revealing anti-QS effects of Lactobacillus acidophilus, Lentilactobacillus kefiri, Lacticaseibacillus rhamnosus and Propionibacterium freudenreichii, including new cheese-associated strains. Our findings also suggest that acetate and propionate excreted by these species are the main factors that interrupt the QS-mediated signaling and subsequent biofilm growth without affecting the cell viability of the C. violaceum reporter. Thus, the present study reports a revised anti-QS screening method to accurately define new bacteria with an ability to combat pathogens in a safe and sustainable way.

Gamow-Teller β decay is forbidden if the number of nodes in the radial wave functions of the initial and final states is different. This Δn=0 requirement plays a major role in the β decay of heavy neutron-rich nuclei, affecting the nucleosynthesis through the increased half-lives of nuclei on the astrophysical r-process pathway below both Z=50 (for N>82) and Z=82 (for N>126). The level of forbiddenness of the Δn=1ν1g9/2→π0g7/2 transition has been investigated from the β− decay of the ground state of 207Hg into the single-proton-hole nucleus 207Tl in an experiment at the ISOLDE Decay Station. From statistical observational limits on possible γ-ray transitions depopulating the π0g7/2−1 state in 207Tl, an upper limit of 3.9×10−3% was obtained for the probability of this decay, corresponding to log⁡ft>8.8 within a 95% confidence limit. This is the most stringent test of the Δn=0 selection rule to date.

The neutron-rich isotopes of palladium have attracted considerable interest in terms of the evolution of the N=82 neutron shell closure and its influence on the r-process nucleosynthesis. In this Letter, we present the first spectroscopic information on the excited states in 125Pd79 and 127Pd81 studied using the EURICA γ-ray spectrometer, following production via in-flight fission of a high-intensity 238U beam at the RIBF facility. New isomeric states with half-lives of 144(4) ns and 39(6) μs have been assigned spins and parities of (23/2+) and (19/2+) in 125Pd and 127Pd, respectively. The observed level properties are compared to a shell-model calculation, suggesting the competition between proton excitations and neutron excitations in the proton-hole and neutron-hole systems in the vicinity of the doubly magic nucleus 132Sn.

Excited states in 63,65,67Mn were studied via in-beam γ-ray spectroscopy following knockout reactions from 68Fe. Similar level schemes, consisting of the 11/2−, 9/2−, 7/2− and 5/2g.s.− level sequence, connected by I→I−1 transitions, were established, the first time for 65,67Mn. Their level structures show features consistent with strongly-coupled rotational bands with K=5/2. State-of-the-art shell-model calculations with the modified LNPS effective interaction reproduce the observed levels remarkably well and suggest the dominance of 4-particle-4-hole neutron configurations for all the states. The data on the low-lying excited states of odd-mass 53−67Mn provide a textbook example of nuclear structure evolution from weak coupling through decoupling to strong coupling along a single isotopic chain on the n-rich side of the β stability line. These results help to deepen our understanding of the N=40 “island of inversion”. Keywords: In-beam γ-ray spectroscopy, “Island of inversion” around N=40, Strong coupling, Structure evolution

The low-lying structures of the midshell νg9/2 Ni isotopes 72Ni and 74Ni have been investigated at the RIBF facility in RIKEN within the EURICA collaboration. Previously unobserved low-lying states were accessed for the first time following β decay of the mother nuclei 72Co and 74Co. As a result, we provide a complete picture in terms of the seniority scheme up to the first (8+) levels for both nuclei. The experimental results are compared to shell-model calculations in order to define to what extent the seniority quantum number is preserved in the first neutron g9/2 shell. We find that the disappearance of the seniority isomerism in the (81+) states can be explained by a lowering of the seniority-four (6+) levels as predicted years ago. For 74Ni, the internal de-excitation pattern of the newly observed (62+) state supports a restoration of the normal seniority ordering up to spin J=4. This property, unexplained by the shell-model calculations, is in agreement with a dominance of the single-particle spherical regime near 78Ni.

We report on the measurement of new low-lying states in the neutron-rich 81,82,83,84Zn nuclei via in-beam γ-ray spectroscopy. These include the 41+→21+ transition in 82Zn, the 21+→0g.s.+ and 41+→21+ transitions in 84Zn, and low-lying states in 81,83Zn were observed for the first time. The reduced E(21+) energies and increased E(41+)/E(2+1) ratios at N=52, 54 compared to those in 80Zn attest that the magicity is confined to the neutron number N=50 only. The deduced level schemes are compared to three state-of-the-art shell model calculations and a good agreement is observed with all three calculations. The newly observed 2+ and 4+ levels in 84Zn suggest the onset of deformation towards heavier Zn isotopes, which has been incorporated by taking into account the upper sdg orbitals in the Ni78-II and the PFSDG-U models.

A new high-spin isomer in the neutron-rich nucleus 128Cd was populated in the projectile fission of a 238U beam at the Radioactive Isotope Beam Factory at RIKEN. A half-life of T1/2=6.3(8) ms was measured for the new state which was tentatively assigned a spin/parity of (15−). The experimental results are compared to shell model calculations performed using state-of-the-art realistic effective interactions and to the neighbouring nucleus 129Cd. In the present experiment no evidence was found for the decay of a 18+ E6 spin-trap isomer, based on the complete alignment of the two-neutron and two-proton holes in the 0h11/2 and the 0g9/2 orbit, respectively, which is predicted to exist by the shell model.

The level structures of 70Co and 70Ni, populated from the β decay of 70Fe, have been investigated using β-delayed γ-ray spectroscopy following in-flight fission of a 238U beam. The experimental results are compared to Monte-Carlo Shell-Model calculations including the pf+g9/2+d5/2 orbitals. The strong population of a (1+) state at 274 keV in 70Co is at variance with the expected excitation energy of ∼1 MeV from near spherical single-particle estimates. This observation indicates a dominance of prolate-deformed intruder configurations in the low-lying levels, which coexist with the normal near spherical states. It is shown that the β decay of the neutron-rich A=70 isobars from the new island of inversion to the Z=28 closed-shell regime progresses in accordance with a newly reported type of shell evolution, the so-called Type II, which involves many particle-hole excitations across energy gaps.

The neutron-rich dysprosium isotopes 168Dy102 and 169Dy103 have been investigated using the EURICA γ-ray spectrometer, following production via in-flight fission of a high-intensity uranium beam in conjunction with isotope separation through the BigRIPS separator at RIBF in RIKEN Nishina Center. For 168Dy, a previously unreported isomer with a half-life of 0.57(7) μs has been identified at an excitation energy of 1378 keV, and its presence affirmed independently using γ-γ-γ coincidence data taken with Gammasphere via two-proton transfer from an enriched 170Er target performed at Argonne National Laboratory. This isomer is assigned Jπ=Kπ=(4−) based on the measured transition strengths, decay patterns, and the energy systematics for two-quasiparticle states in N=102 isotones. The underlying mechanism of two-quasiparticle excitations in the doubly midshell region is discussed in comparison with the deformed QRPA and multi-quasiparticle calculations. In 169Dy, the B(E2) value for the transition de-exciting the previously unreported Kπ=(1/2−) isomeric state at 166 keV to the Kπ=(5/2−) ground state is approximately two orders of magnitude larger than the E2 strength for the corresponding isomeric-decay transition in the N=103 isotone 173Yb, suggesting the presence of a significant γ-vibrational admixture with a dominant neutron one-quasiparticle component in the isomeric state.

A detailed study of the structure of the doubly mid-shell nucleus Dy104166170 has been carried out, following isomeric and β decay. We have measured the yrast band up to the spin-parity Jπ=6+ state, the K=2 γ-vibration band up to the 5+ state, a low-lying negative-parity band based on a 2− state that could be a candidate for the lowest energy octupole vibration state within this nucleus, and a candidate for the Kπ=6+ two quasi-particle isomer. This state was determined to have an excitation energy of 1643.91(23) keV and a half life of 0.99(4) μs, with a reduced hindrance for its decay to the ground-state band an order of magnitude lower than predicted by NpNn systematics. This is interpreted as being due to γ-vibrational mixing from a near degeneracy of the isomer and the 6+ state of the γ band. Furthermore, the parent nucleus 170Tb has been determined to have a half-life of 0.91(−13+18) s with a possible spin-parity of 2−. Keywords: K isomer, Dysprosium, Mid-shell, γ-Ray spectroscopy

The level structure of 172Dy has been investigated for the first time by means of decay spectroscopy following in-flight fission of a 238U beam. A long-lived isomeric state with T1/2=0.71(5) s and Kπ=8− has been identified at 1278 keV, which decays to the ground-state and γ-vibrational bands through hindered electromagnetic transitions, as well as to the daughter nucleus 172Ho via allowed β decays. The robust nature of the Kπ=8− isomer and the ground-state rotational band reveals an axially-symmetric structure for this nucleus. Meanwhile, the γ-vibrational levels have been identified at unusually low excitation energy compared to the neighboring well-deformed nuclei, indicating the significance of the microscopic effect on the non-axial collectivity in this doubly mid-shell region. The underlying mechanism of enhanced γ vibration is discussed in comparison with the deformed Quasiparticle Random-Phase Approximation based on a Skyrme energy-density functional.

The decay of a new four-quasiparticle isomeric state in 160Sm has been observed using γ-ray spectroscopy at the RIBF, RIKEN. The four-quasiparticle state is assigned a 2π⊗2ν π52−[532], π52+[413], ν52−[523], ν72+[633] configuration. The half-life of this (11+) state is measured to be 1.8(4) μs. The (11+) isomer decays into a rotational band structure, based on a (6−) ν52−[523]⊗ν72+[633] bandhead, consistent with the gK−gR values. This decays to a (5−) two-proton quasiparticle state, which in turn decays to the ground state band. Potential energy surface and blocked-BCS calculations were performed in the deformed midshell region around 160Sm. They reveal a significant influence from β6 deformation and that 160Sm is the best candidate for the lightest four-quasiparticle K isomer to exist in this region. The relationship between reduced hindrance and isomer excitation energy for E1 transitions from multiquasiparticle states is considered with the new data from 160Sm. The E1 data are found to agree with the existing relationship for E2 transitions.

Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, with 80% of these infections being caused by a bacterial biofilm. The insertion of a foreign material usually elicits inflammation, which can result in hampered antimicrobial capacity of the host immunity due to the effort of immune cells being directed to degrade the material. The ineffective clearance by immune cells is a perfect opportunity for bacteria to attach and form a biofilm. In this study, we analyzed the antibiofilm capacity of three naturally derived biofilm inhibitors when combined with immune cells in order to assess their applicability in implantable titanium devices and low-density polyethylene (LDPE) endotracheal tubes. To this end, we used a system based on the coculture of HL-60 cells differentiated into polymorphonuclear leukocytes (PMNs) and Staphylococcus aureus (laboratory and clinical strains) on titanium, as well as LDPE surfaces. Out of the three inhibitors, the one coded DHA1 showed the highest potential to be incorporated into implantable devices, as it displayed a combined activity with the immune cells, preventing bacterial attachment on the titanium and LDPE. The other two inhibitors seemed to also be good candidates for incorporation into LDPE endotracheal tubes.

Biofilm-mediated infection is a major cause of bone prosthesis failure. The lack of molecules able to act in biofilms has driven research aimed at identifying new anti-biofilm agents via chemical screens. However, to be able to accommodate a large number of compounds, the testing conditions of these screenings end up being typically far from the clinical scenario. In this study, we assess the potential applicability of three previously discovered anti-biofilm compounds to be part of implanted medical devices by testing them on in vitro systems that more closely resemble the clinical scenario. To that end, we used a competition model based on the co-culture of SaOS-2 mammalian cells and Staphylococcus aureus (collection and clinical strains) on a titanium surface, as well as titanium pre-conditioned with high serum protein concentration. Additionally, we studied whether these compounds enhance the previously proven protective effect of pre-incubating titanium with SaOS-2 cells. Out of the three, DHA1 was the one with the highest potential, showing a preventive effect on bacterial adherence in all tested conditions, making it the most promising agent for incorporation into bone implants. This study emphasizes and demonstrates the importance of using meaningful experimental models, where potential antimicrobials ought to be tested for the protection of biomaterials in translational applications.

The β decays Mn68→Fe68, Mn69→Fe69 and Mn70→Fe70 have been measured at the RIBF facility at RIKEN using the EURICA γ spectrometer combined with an active stopper consisting of a stack of Si detectors. The nuclei were produced as fission fragments from a beam of 238U at a bombarding energy of 345 MeV/nucleon impinging on a Be target and selected using the BigRIPS separator. Half-lives and β-delayed neutron emission probabilities have been extracted for these decays, together with first experimental information on excited states populated in 69,70Fe. The data indicate a continuously increasing deformation for Fe isotopes up to A=70. This is interpreted, as for Cr isotopes, in terms of the interplay between the quadrupole correlations of the ν1d5/2 and ν0g9/2 orbitals and the monopole component of the π0f7/2–ν0f5/2 interaction.

The first fast-timing measurements from nuclides produced via the in-flight fission mechanism are reported. The lifetimes of the first 2+ states in 104,106Zr nuclei have been measured via β-delayed γ-ray timing of stopped radioactive isotope beams. An improved precision for the lifetime of the 21+ state in 104Zr was obtained, τ(21+)=2.90−20+25 ns, as well as a first measurement of the 21+ state in 106Zr, τ(21+)=2.60−15+20 ns, with corresponding reduced transition probabilities of B(E2;21+→0g.s.+)=0.39(2) e2b2 and 0.31(1) e2b2, respectively. Comparisons of the extracted ground-state deformations, β2=0.39(1) (104Zr) and β2=0.36(1) (106Zr) with model calculations indicate a persistence of prolate deformation. The data show that 104Zr is the most deformed of the neutron-rich Zr isotopes measured so far.

The decay of an isomeric state in the neutron-rich nucleus 129Cd has been observed via the detection of internal conversion and Compton electrons providing first experimental information on excited states in this nucleus. The isomer was populated in the projectile fission of a 238U beam at the Radioactive Isotope Beam Factory at RIKEN. From the measured yields of γ-rays and internal conversion electrons, a multipolarity of E3 was tentatively assigned to the isomeric transition. A half-life of T1/2=3.6(2) ms was determined for the new state which was assigned a spin of (21/2+), based on a comparison to shell model calculations performed using state-of-the-art realistic effective interactions. Keywords: Isomeric decays, Transition strengths, Shell model calculations

BackgroundHuman lymphocyte antigen B-associated transcript 5 (BAT5, also known as ABHD16A) is a poorly characterized 63 kDa protein belonging to the α/β-hydrolase domain (ABHD) containing family of metabolic serine hydrolases. Its natural substrates and biochemical properties are unknown.Methodology/principal findingsAmino acid sequence comparison between seven mammalian BAT5 orthologs revealed that the overall primary structure was highly (≥95%) conserved. Activity-based protein profiling (ABPP) confirmed successful generation of catalytically active human (h) and mouse (m) BAT5 in HEK293 cells, enabling further biochemical characterization. A sensitive fluorescent glycerol assay reported hBAT5-mediated hydrolysis of medium-chain saturated (C14:0), long-chain unsaturated (C18:1, C18:2, C20:4) monoacylglycerols (MAGs) and 15-deoxy-Δ12,14-prostaglandin J2-2-glycerol ester (15d-PGJ2-G). In contrast, hBAT5 possessed only marginal diacylglycerol (DAG), triacylglycerol (TAG), or lysophospholipase activity. The best MAG substrates were 1-linoleylglycerol (1-LG) and 15d-PGJ2-G, both exhibiting low-micromolar Km values. BAT5 had a neutral pH optimum and showed preference for the 1(3)- vs. 2-isomers of MAGs C18:1, C18:2 and C20:4. Inhibitor profiling revealed that β-lactone-based lipase inhibitors were nanomolar inhibitors of hBAT5 activity (palmostatin B > tetrahydrolipstatin > ebelactone A). Moreover, the hormone-sensitive lipase inhibitor C7600 (5-methoxy-3-(4-phenoxyphenyl)-3H-[1], [3], [4]oxadiazol-2-one) was identified as a highly potent inhibitor (IC50 8.3 nM). Phenyl and benzyl substituted analogs of C7600 with increased BAT5 selectivity were synthesized and a preliminary SAR analysis was conducted to obtain initial insights into the active site dimensions.Conclusions/significanceThis study provides an initial characterization of BAT5 activity, unveiling the biochemical and pharmacological properties with in vitro substrate preferences and inhibitor profiles. Utilization of glycerolipid substrates and sensitivity to lipase inhibitors suggest that BAT5 is a genuine lipase with preference for long-chain unsaturated MAGs and could in this capacity regulate glycerolipid metabolism in vivo as well. This preliminary SAR data should pave the way towards increasingly potent and BAT5-selective inhibitors.