Implementation and impact of an antibiotic control program and multidrug-resistant bacterial colonization in a liver transplant unit.

INTRODUCTION: infections by multidrug-resistant bacteria are a major cause of morbidity and mortality in transplant patients. OBJECTIVE: a retrospective single-center study was performed to evaluate the implementation of an Antimicrobial Treatment Optimization Program (PROA) on multidrug-resistant bacteria colonization and infection after liver transplant (LT). METHODS: colonization by multidrug-resistant bacteria and infections during the first year after a liver transplant were analyzed in a group of 76 transplanted patients in two stages, before and after PROA (2016-2019). Clinical variables related to infection, readmissions and survival one year after the liver transplant were analyzed. RESULTS: there was good adherence to the PROA. Infection was the most frequent cause for readmission during the first year after the liver transplant. Incidence of infections was similar during both periods (mean of 1.25 and 1.5 episodes of bacterial infection per patient/year, respectively) with 19 bacterial infectious episodes, six by hospital-acquired multidrug-resistant and extensively drug-resistant (MDR-XDR) bacteria in the pre-PROA stage, and 18 bacterial infectious episodes, five by MDR-XDR in the post-PROA stage. A 37 % decrease of post-TH of rectal colonization by MDR-XDR after liver transplant was observed during 2019. CONCLUSIONS: epidemiological surveillance policies and antibiotic optimization are key to control the increase of colonization and infection by multidrug-resistant bacteria in liver transplant units. Long-term studies are needed to better evaluate the impact of these programs.

SARS-COV-2 Infection in People Living with HIV: Experience from a Tertiary Hospital in Madrid.

Since SAR-COV-2 infection emerged and spread worldwide, little is known about its impact on people living with human immunodeficiency virus (HIV). We performed a single-center retrospective study to describe the potential particularities and risk factors for respiratory failure (RF) in that population. This single-center retrospective study included patients infected with HIV, whose current follow-up is run in this center, above18 years of age, with diagnosis of SARS-CoV-2 infection between March 5, 2020 and April 15, 2021. We collected data regarding HIV immunological and virological status, main epidemiological characteristics, as well as those conditions considered to potentially influence in SARS-CoV-2 evolution; and clinical, microbiological, radiological, respiratory status, and survival concerning coronavirus disease 2019 (COVID-19). We compared all that, for patients with and without RF and performed a logistic regression for suspected risk factors for RF. One hundred seventy-seven HIV patients were diagnosed from COVID-19 (mean age 53.8 years, 81.3% male). At diagnosis, 95.5% were receiving ART and 91.3% had undetectable viral load, with median CD4 count of 569 cells/µL. One hundred thirty-eight patients (78.4%) had symptoms, 44 (25%) developed RF and 53 (31%) developed bilateral pneumonia. The most commonly used treatments were: steroids (26.7%) and hydroxychloroquine (13.1%). When comparing patients with and without RF, we found statistically significant differences for 20 of the analyzed variables such as age (p < .001) and CD4 (p 0.002), and route of HIV transmission by intravenous drug users IVDU (p 0.002) were determined. In multivariate analysis, age [odds ratio (OR) 1.095] and CD4 count less than 350 cells/µL (OR 3.36) emerged as risk factor for RF. People living with HIV whose CD4 count is <350 cells are at higher risk of developing RF when infected by SARS-CoV-2.

Magnetic, Mechanically Interlocked Porphyrin-Carbon Nanotubes for Quantum Computation and Spintronics.

Atomic-scale reproducibility and tunability endorse magnetic molecules as candidates for spin qubits and spintronics. A major challenge is to implant those molecular spins into circuit geometries that may allow one, two, or a few spins to be addressed in a controlled way. Here, the formation of mechanically bonded, magnetic porphyrin dimeric rings around carbon nanotubes (mMINTs) is presented. The mechanical bond places the porphyrin magnetic cores in close contact with the carbon nanotube without disturbing their structures. A combination of spectroscopic techniques shows that the magnetic geometry of the dimers is preserved upon formation of the macrocycle and the mMINT. Moreover, the metallic core selection determines the spin location in the mMINT. The suitability of mMINTs as qubits is explored by measuring their quantum coherence times (Tm). Formation of the dimeric ring preserves the Tm found in the monomer, which remains in the µs scale for mMINTs. The carbon nanotube is used as vessel to place the molecules in complex circuits. This strategy can be extended to other families of magnetic molecules. The size and composition of the macrocycle can be tailored to modulate magnetic interactions between the cores and to introduce magnetic asymmetries (heterometallic dimers) for more complex molecule-based qubits.

Nanoporous Anodic Alumina-Based Sensor for miR-99a-5p Detection as an Effective Early Breast Cancer Diagnostic Tool.

Circulating microRNAs have emerged as potential diagnostic biomarkers. The deregulation of the microRNA miR-99a-5p has been previously described as an effective biomarker of early breast cancer. Herein, we present a new nanoporous anodic alumina (NAA)-based biosensor that can detect plasma miR-99a-5p with high sensitivity and selectivity. NAA pores are loaded with rhodamine B and capped with a specific oligonucleotide that is able to block cargo release until the target is present. In the presence of miR-99a-5p, the capping oligonucleotide recognizes the miR-99a-5p sequence and displaces it allowing the release of the encapsulated dye. This method is able to successfully distinguish healthy controls from breast cancer patients, even at early stages with high efficiency, showing the presented system as a promising tool for breast cancer detection.

Circulating miR-99a-5p Expression in Plasma: A Potential Biomarker for Early Diagnosis of Breast Cancer.

MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analysed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. MiR-99a-5p expression levels were determined by quantitative real-time PCR in three independent cohorts of patients: (I) Discovery cohort: breast cancer tissues (n = 103) and healthy breast tissues (n = 26); (II) Testing cohort: plasma samples from 105 patients and 98 healthy donors; (III) Validation cohort: plasma samples from 89 patients and 85 healthy donors. Our results demonstrated that miR-99a-5p was significantly downregulated in breast cancer tissues compared to healthy breast tissues. Conversely, miR-99a-5p levels were significantly higher in breast cancer patients than in healthy controls in plasma samples from both testing and validation cohorts, and ROC curve analysis revealed that miR-99a-5p has good diagnostic potential even to detect early breast cancer. In conclusion, miR-99a-5p's deregulated expression distinguished healthy patients from breast cancer patients in two different types of samples (tissues and plasma). Interestingly, expression levels in plasma were significantly lower in healthy controls than in early-stage breast cancer patients. Our findings suggest circulating miR-99a-5p as a novel promising non-invasive biomarker for breast cancer detection.

Amplification of enantiomeric excess by dynamic inversion of enantiomers in deracemization of Au38 clusters.

Symmetry breaking and amplification processes have likely played a fundamental role in the development of homochirality on earth. Such processes have not been much studied for inorganic matter at the nanoscale. Here, we show that the balance between left- and right-handed intrinsically chiral metal clusters can be broken by adsorbing a small amount of a chiral molecule in its ligand shell. We studied the amplification of enantiomeric excess of the Au38(2-PET)24 cluster (2-PET = 2-phenylethylthiolate). By exchanging a small fraction of the achiral 2-PET ligand by chiral R-1,1'-binaphthyl-2,2'-dithiol (R-BINAS), a mixture of species is obtained composed of anticlockwise (A) and clockwise (C) versions of Au38(2-PET)24 and Au38(2-PET)22(R-BINAS)1. At 70 °C, the system evolves towards the anticlockwise clusters at the expense of the clockwise antipode. It is shown that the interplay between the diastereospecific ligand exchange, which introduces selectivity but does not change the A/C ratio, and the fast racemization of the Au38(2-PET)24 is at the origin of this observation.

Hydrogen-bonded host-guest systems are stable in ionic liquids.

We show that H-bonded host-guest systems associate in ionic liquids (ILs), pure salts with melting point below room temperature, in which dipole-dipole electrostatic interactions should be negligible in comparison with dipole-charge interactions. Binding constants (Ka) obtained from titrations of four H-bonded host-guest systems in two organic solvents and two ionic liquids yield smaller yet comparable Ka values in ionic liquids than in organic solvents. We also detect the association event using force spectroscopy, which confirms that the binding is not solely due to (de)solvation processes. Our results indicate that classic H-bonded host-guest supramolecular chemistry takes place in ILs. This implies that strong H-bonds are only moderately affected by surroundings composed entirely of charges, which can be interpreted as an indication that the balance of Coulombic to covalent forces in strong H-bonds is not tipped towards the former.

NOTCH signalling in ovarian cancer angiogenesis.

The Notch signalling pathway is involved in the new vessel formation process by regulating tip and stalk cells, which are key cells in the sprout formation. This process is essential in both normal ovary and cancer angiogenesis and is regulated by Notch-VEGF crosstalk. Furthermore, Notch has been linked in ovary with stem cell maintenance and epithelial mesenchymal transition processes. Dysregulation of the Notch pathway is frequent in ovarian cancer (OC) and it has been associated with impaired survival and advanced stages or lymph node involvement. Notch also plays a role in chemoresistance to platinum. In this context, this pathway has emerged as an attractive target for precision medicine in OC. Two main targets of this pathway concentrate the clinical development of compounds blocking Notch: gamma secretase and Delta-like ligand 4. Most of the clinical trials including OC patients have been developed in phase I or phase Ib. Despite being in an early phase, both of these compounds, navicixizumab or demcizumab, two monoclonal antibodies targeting Dll4, showed promising efficacy data in platinum-resistant OC patients in recent studies. This review will focus on the mechanisms of the Notch pathway with special interest in angiogenesis regulation and the implication of Notch as a potential therapeutic target in OC.

Transformation from [Au25(SCH2CH2CH2CH3)18]0 to Au28(SCH2CH(CH3)Ph)21 gold nanoclusters: gentle conditions is enough.

Herein we report the transformation of [Au25(SR)18]0 into Au28(SR)21 induced by ligand exchange reaction. In contrast to other reported cluster transformations, which proceed at elevated temperature and large excess of incoming ligands, the transformation reported here occurs under mild conditions (room temperature, very low thiol excess) with a chiral ligand. A difference of one methyl group between incoming and leaving thiol is sufficient to induce the transformation. To the best of our knowledge the Au28(SR)21 cluster has not been isolated before.

Vibrational Properties of Thiolate-Protected Gold Nanoclusters.

Over recent years, the field of thiolate-protected gold nanoclusters has made remarkable progress. The successful determination of the structure of some of these clusters by X-ray crystallography was a milestone in this field. X-ray crystallography is arguably the most important technique in the field up to now, and it enabled the study of structure evolution as a function of cluster size. It also shed light on the structure of the Au-S interface. Recently, it has been realized that thiolate-protected gold clusters are very dynamic systems. Metal atoms and ligands can exchange easily between clusters. Furthermore, the adsorbed ligands bear conformational dynamics. Such dynamic effects call for experimental methods that can cope with it. Future efforts in this field will be directed toward applications of thiolate-protected clusters, and many of them will rely on dissolved clusters. Therefore, structure determination in solution is an important issue, though it is very challenging. The structure of the metal core and the Au-S interface is not expected to change in solution with respect to the crystal. However, the structure of the adsorbed ligand itself is sensitive to the environment and may be different in the solid state and in solution, as has been shown in fact in the past. It is this (dynamic) structure of the ligand that determines the interaction between the cluster and its environment, which is crucial, for example, for sensing applications. Vibrational spectroscopy is a promising technique to characterize thiolate-protected clusters in different environments. A vibrational spectrum is sensitive to structure (conformation) although this information is often "hidden" in the spectrum, requiring detailed analysis and support from theory to be deciphered. Compared to other techniques like UV-vis spectroscopy and mass spectrometry, vibrational spectroscopy was not extensively used in the field of thiolate-protected clusters, but we believe that the technique will be very valuable for the future developments in the field. We have used vibrational spectroscopy to investigate thiolate-protected gold clusters for mainly two lines of research. In the first, we studied in detail the low energy region of the vibrational spectrum, in particular the Au-S vibrational modes, in order to understand the structure sensitivity. It emerges that the Au-S vibrational spectrum is indeed sensitive to the structure of the interface but also to other factors, especially the organic part of the thiol, in a complex way. The ability to directly correlate structure, from X-ray crystallography, and vibrational spectra for thiolate-protected clusters, should lead to a database that will help in the future the structure determination of the Au-S interface by vibrational spectroscopy for systems where direct structure determination is not possible, for example, for flat surfaces. A second line of research focused on the determination of the structure of the adsorbed ligands for dissolved clusters. Such information is mostly extracted by the comparison of theoretical and calculated spectra for different conformers. In this respect, vibrational circular dichroism (VCD) is particularly powerful as it strongly depends on the conformation, more than conventional infrared spectroscopy. VCD can be applied to chiral nonracemic compounds, and it is a sensitive probe for chirality. Using this method, it was possible to demonstrate that a cluster can transfer its chirality to achiral thiolate ligands. In this Account, we summarize the possibilities and challenges of vibrational spectroscopy in the field of thiolate-protected clusters.

Interfacing porphyrins and carbon nanotubes through mechanical links.

We describe the synthesis of rotaxane-type species composed of macrocyclic porphyrin rings mechanically interlocked with SWCNT threads. The formation of mechanically interlocked SWCNTs (MINTs) proceeds with chiral selectivity, and was confirmed by spectroscopic and analytical techniques and adequate control experiments, and corroborated by high-resolution electron microscopy. From a thorough characterization of the MINTs through UV-vis-NIR absorption, fluorescence, Raman, and transient absorption spectroscopy we analyse in detail the electronic interactions of the porphyrins and the SWCNTs in the ground and excited states.

Positive and negative regulation of carbon nanotube catalysts through encapsulation within macrocycles.

One of the most attractive applications of carbon nanomaterials is as catalysts, due to their extreme surface-to-volume ratio. The substitution of C with heteroatoms (typically B and N as p- and n-dopants) has been explored to enhance their catalytic activity. Here we show that encapsulation within weakly doping macrocycles can be used to modify the catalytic properties of the nanotubes towards the reduction of nitroarenes, either enhancing it (n-doping) or slowing it down (p-doping). This artificial regulation strategy presents a unique combination of features found in the natural regulation of enzymes: binding of the effectors (the macrocycles) is noncovalent, yet stable thanks to the mechanical link, and their effect is remote, but not allosteric, since it does not affect the structure of the active site. By careful design of the macrocycles' structure, we expect that this strategy will contribute to overcome the major hurdles in SWNT-based catalysts: activity, aggregation, and specificity.

Redox-Active Chiroptical Switching in Mono- and Bis-Iron Ethynylcarbo[6]helicenes Studied by Electronic and Vibrational Circular Dichroism and Resonance Raman Optical Activity.

Introducing one or two alkynyl-iron moieties onto a carbo[6]helicene results in organometallic helicenes (2 a,b) that display strong chiroptical activity combined with efficient redox-triggered switching. The neutral and oxidized forms have been studied in detail by electronic and vibrational circular dichroism, as well as by Raman optical activity (ROA) spectroscopy. The experimental results were analyzed and spectra were assigned with the help of first-principles calculations. In particular, a recently developed method for ROA calculations under resonance conditions has been used to study the intricate resonance effects on the ROA spectrum of mono-iron ethynylhelicene 2 a.

Reversible dispersion and release of carbon nanotubes via cooperative clamping interactions with hydrogen-bonded nanorings.

Due to their outstanding electronic and mechanical properties, single-walled carbon nanotubes (SWCNTs) are promising nanomaterials for the future generation of optoelectronic devices and composites. However, their scarce solubility limits their application in many technologies that demand solution-processing of high-purity SWCNT samples. Although some non-covalent functionalization approaches have demonstrated their utility in extracting SWCNTs into different media, many of them produce short-lived dispersions or ultimately suffer from contamination by the dispersing agent. Here, we introduce an unprecedented strategy that relies on a cooperative clamping process. When mixing (6,5)SWCNTs with a dinucleoside monomer that is able to self-assemble in nanorings via Watson-Crick base-pairing, a synergistic relationship is established. On one hand, the H-bonded rings are able to associate intimately with SWCNTs by embracing the tube sidewalls, which allows for an efficient SWCNT debundling and for the production of long-lasting SWCNT dispersions of high optical quality along a broad concentration range. On the other, nanoring stability is enhanced in the presence of SWCNTs, which are suitable guests for the ring cavity and contribute to the establishment of multiple cooperative noncovalent interactions. The inhibition of these reversible interactions, by just adding, for instance, a competing solvent for hydrogen-bonding, proved to be a simple and effective method to recover the pristine nanomaterial with no trace of the dispersing agent.

Sequential Induction of Chirality in Helical Polymers: From the Stereocenter to the Achiral Solvent.

Several steps of chiral induction have been detected in poly(phenylacetylene)s among their different hierarchical levels of chirality by vibrational circular dichroism, namely, (i) from the stereogenic centers to the innermost polyacetylene helical covalent backbone (helixint), (ii) from this to the external helix (helixext) formed by the side phenyl pendants that form a complementary helix or counter-helix, and (iii) from this pendant helix to the helical solvation sphere (helixsolv.), the last one being observed along this work. The pendant to polyene backbone chiral induction determines the helical structure adopted by the polymer and therefore the solvation helix. This helical structure is promoted by two mechanisms: steric effects and hydrogen bonding. An important finding concerns the demonstration by VCD of how an achiral solvent becomes chirally organized owing to the template effect of the covalent polymer helices, an effect that is silent to other structural techniques such as ECD or AFM and that hence significantly broadens the scope of these previous analyses.

Mechanical measurement of hydrogen bonded host-guest systems under non-equilibrium, near-physiological conditions.

Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of biological systems. We present a new method that exploits the high force resolution of optical tweezers to measure at the single molecule level the mechanical strength of a hydrogen bonded host-guest pair out of equilibrium and under near-physiological conditions. We utilize a DNA reporter to unambiguously isolate single binding events. The Hamilton receptor-cyanuric acid host-guest system is used as a test bed. The force required to dissociate the host-guest system is ∼17 pN and increases with the pulling rate as expected for a system under non-equilibrium conditions. Blocking one of the hydrogen bonding sites results in a significant decrease of the force-to-break by 1-2 pN, pointing out the ability of the method to resolve subtle changes in the mechanical strength of the binding due to the individual H-bonding components. We believe the method will prove to be a versatile tool to address important questions in supramolecular chemistry.

Band-Gap Opening in Metallic Single-Walled Carbon Nanotubes by Encapsulation of an Organic Salt.

The encapsulation of viologen derivatives into metallic single-walled carbon nanotubes (SWNTs) results in the opening of a band gap, making the SWNTs semiconducting. Raman spectroscopy, thermogravimetric analysis, and aberration-corrected high-resolution transmission electron microscopy confirm the encapsulation process. Through the fabrication of field-effect transistor devices, the change of the electronic structure of the tubes from metallic to semiconducting upon the encapsulation is confirmed. The opening of a gap in the band structure of the tubes was not detected in supramolecular controls.

Threading through Macrocycles Enhances the Performance of Carbon Nanotubes as Polymer Fillers.

In this work, we study the reinforcement of polymers by mechanically interlocked derivatives of single-walled carbon nanotubes (SWNTs). We compare the mechanical properties of fibers made of polymers and of composites with pristine SWNTs, mechanically interlocked derivatives of SWNTs (MINTs), and the corresponding supramolecular models. Improvements of both Young's modulus and tensile strength of up to 200% were observed for the polystyrene-MINT samples with an optimized loading of just 0.01 wt %, while the supramolecular models with identical chemical composition and loading showed negligible or even detrimental influence. This behavior is found for three different types of SWNTs and two types of macrocycles. Molecular dynamics simulations show that the polymer adopts an elongated conformation parallel to the SWNT when interacting with MINT fillers, irrespective of the macrocycle chemical nature, whereas a more globular structure is taken upon facing with either pristine SWNTs or supramolecular models. The MINT composite architecture thus leads to a more efficient exploitation of the axial properties of the SWNTs and of the polymer chain at the interface, in agreement with experimental results. Our findings demonstrate that the mechanical bond imparts distinctive advantageous properties to SWNT derivatives as polymer fillers.

Iron Alkynyl Helicenes: Redox-Triggered Chiroptical Tuning in the IR and Near-IR Spectral Regions and Suitable for Telecommunications Applications.

The combination of a bis-alkynyl-helicene moiety with two iron centers leads to novel electroactive species displaying unprecedented redox-triggered chiroptical switching. Upon oxidation, strong changes of vibrational modes (either local or extended coupled modes) are detected by vibrational circular dichroism and Raman optical activity. Remarkably, the sign of the optical rotation at 1.54 µm (that is, at wavelengths typically used for telecommunications) changes upon oxidation while the topology and stereochemistry of the helicene remain unchanged.

[Microbiological diagnosis of bacterial infection associated with delivery and postpartum]. / Diagnóstico microbiológico de la infección bacteriana asociada al parto y puerperio.

The newborn may acquire infections during delivery due to maternal colonization of the birth canal, by microorganisms such as Streptococcus agalactiae that caused early neonatal infection, or acquisition through the placenta, amniotic fluid or birth products. After birth, the newborn that needs hospitalization can develop nosocomial infections during their care and exceptionally through lactation by infectious mastitis or incorrect handling of human milk, which does not require to stop breastfeeding in most cases. It is important and necessary to perform microbiological diagnosis for the correct treatment of perinatal infections, especially relevant in preterm infants with low or very low weight with high mortality rates.