Bistability between π-diradical open-shell and closed-shell states in indeno[1,2-a]fluorene.

Indenofluorenes are non-benzenoid conjugated hydrocarbons that have received great interest owing to their unusual electronic structure and potential applications in nonlinear optics and photovoltaics. Here we report the generation of unsubstituted indeno[1,2-a]fluorene on various surfaces by the cleavage of two C-H bonds in 7,12-dihydroindeno[1,2-a]fluorene through voltage pulses applied by the tip of a combined scanning tunnelling microscope and atomic force microscope. On bilayer NaCl on Au(111), indeno[1,2-a]fluorene is in the neutral charge state, but it exhibits charge bistability between neutral and anionic states on the lower-workfunction surfaces of bilayer NaCl on Ag(111) and Cu(111). In the neutral state, indeno[1,2-a]fluorene exhibits one of two ground states: an open-shell π-diradical state, predicted to be a triplet by density functional and multireference many-body perturbation theory calculations, or a closed-shell state with a para-quinodimethane moiety in the as-indacene core. We observe switching between open- and closed-shell states of a single molecule by changing its adsorption site on NaCl.

The effect of water on gold supported chiral graphene nanoribbons: rupture of conjugation by an alternating hydrogenation pattern.

In the last few years we have observed a breakpoint in the development of graphene-derived technologies, such as liquid phase filtering and their application to electronics. In most of these cases, they imply exposure of the material to solvents and ambient moisture, either in the fabrication of the material or the final device. The present study demonstrates the sensitivity of graphene nanoribbon (GNR) zigzag edges to water, even in extremely low concentrations. We have addressed the unique reactivity of (3,1)-chiral GNR with moisture on Au(111). Water shows a reductive behaviour, hydrogenating the central carbon of the zigzag segments. By combining scanning tunnelling microscopy (STM) with simulations, we demonstrate how their reactivity reaches a thermodynamic limit when half of the unit cells are reduced, resulting in an alternating pattern of hydrogenated and pristine unit cells starting from the terminal segments. Once a quasi-perfect alternation is reached, the reaction stops regardless of the water concentration. The hydrogenated segments limit the electronic conjugation of the GNR, but the reduction can be reversed both by tip manipulation and annealing. Selective tip-induced dehydrogenation allowed the stabilization of radical states at the edges of the ribbons, while the annealing of the sample completely recovered the original, pristine GNR.

Introducing Design Strategies to Preserve N-Heterocycles Throughout the On-Surface Synthesis of Graphene Nanostructures.

Despite the impressive advances in the synthesis of atomically precise graphene nanostructures witnessed during the last decade, advancing in compositional complexity faces major challenges. The concept of introducing the desired functional groups or dopants in the molecular precursor often fails due to their lack of stability during the reaction path. Here, a study on the stability of different pyridine and pyrimidine moieties during the on-surface synthesis of graphene nanoribbons on Au(111) is presented. Combining bond-resolved scanning tunneling microscopy with X-ray photoelectron spectroscopy, the thermal evolution of the nitrogen dopants throughout the whole reaction sequence is tracked. A comparative experimental and ab initio electronic characterization confirms the presence of dopants in the final structures, revealing also that the pyridinic nitrogen leads to a significant band downshift. The results demonstrate that, by using synthetic strategies to lower the reaction temperatures, one can preserve specific N-heterocycles throughout all the reaction steps of the synthesis of graphene nanoribbons and beyond the interibbon coupling reaction that leads to nanoporous graphene.

Dynamics of efflux pumps in antimicrobial resistance, persistence, and community living of Vibrionaceae.

The marine bacteria of the Vibrionaceae family are significant from the point of view of their role in the marine geochemical cycle, as well as symbionts and opportunistic pathogens of aquatic animals and humans. The well-known pathogens of this group, Vibrio cholerae, V. parahaemolyticus, and V. vulnificus, are responsible for significant morbidity and mortality associated with a range of infections from gastroenteritis to bacteremia acquired through the consumption of raw or undercooked seafood and exposure to seawater containing these pathogens. Although generally regarded as susceptible to commonly employed antibiotics, the antimicrobial resistance of Vibrio spp. has been on the rise in the last two decades, which has raised concern about future infections by these bacteria becoming increasingly challenging to treat. Diverse mechanisms of antimicrobial resistance have been discovered in pathogenic vibrios, the most important being the membrane efflux pumps, which contribute to antimicrobial resistance and their virulence, environmental fitness, and persistence through biofilm formation and quorum sensing. In this review, we discuss the evolution of antimicrobial resistance in pathogenic vibrios and some of the well-characterized efflux pumps' contributions to the physiology of antimicrobial resistance, host and environment survival, and their pathogenicity.

Emergence of π-Magnetism in Fused Aza-Triangulenes: Symmetry and Charge Transfer Effects.

On-surface synthesis has paved the way toward the fabrication and characterization of conjugated carbon-based molecular materials that exhibit π-magnetism such as triangulenes. Aza-triangulene, a nitrogen-substituted derivative, was recently shown to display rich on-surface chemistry, offering an ideal platform to investigate structure-property relations regarding spin-selective charge transfer and magnetic fingerprints. Herein, we study electronic changes upon fusion of single molecules into larger dimeric derivatives. We show that the closed-shell structure of aza-triangulene on Ag(111) leads to closed-shell dimers covalently coupled through sterically accessible carbon atoms. Meanwhile, its open-shell structure on Au(111) leads to coupling via atoms displaying a high spin density, resulting in symmetric or asymmetric products. Interestingly, whereas all dimers on Au(111) exhibit similar charge transfer properties, only asymmetric ones show magnetic fingerprints due to spin-selective charge transfer. These results expose clear relationships among molecular symmetry, charge transfer, and spin states of π-conjugated carbon-based nanostructures.

Functional Roles of the Conserved Amino Acid Sequence Motif C, the Antiporter Motif, in Membrane Transporters of the Major Facilitator Superfamily.

The biological membrane surrounding all living cells forms a hydrophobic barrier to the passage of biologically important molecules. Integral membrane proteins called transporters circumvent the cellular barrier and transport molecules across the cell membrane. These molecular transporters enable the uptake and exit of molecules for cell growth and homeostasis. One important collection of related transporters is the major facilitator superfamily (MFS). This large group of proteins harbors passive and secondary active transporters. The transporters of the MFS consist of uniporters, symporters, and antiporters, which share similarities in structures, predicted mechanism of transport, and highly conserved amino acid sequence motifs. In particular, the antiporter motif, called motif C, is found primarily in antiporters of the MFS. The antiporter motif's molecular elements mediate conformational changes and other molecular physiological roles during substrate transport across the membrane. This review article traces the history of the antiporter motif. It summarizes the physiological evidence reported that supports these biological roles.

Detecting the spin-polarization of edge states in graphene nanoribbons.

Low dimensional carbon-based materials can show intrinsic magnetism associated to p-electrons in open-shell π-conjugated systems. Chemical design provides atomically precise control of the π-electron cloud, which makes them promising for nanoscale magnetic devices. However, direct verification of their spatially resolved spin-moment remains elusive. Here, we report the spin-polarization of chiral graphene nanoribbons (one-dimensional strips of graphene with alternating zig-zag and arm-chair boundaries), obtained by means of spin-polarized scanning tunnelling microscopy. We extract the energy-dependent spin-moment distribution of spatially extended edge states with π-orbital character, thus beyond localized magnetic moments at radical or defective carbon sites. Guided by mean-field Hubbard calculations, we demonstrate that electron correlations are responsible for the spin-splitting of the electronic structure. Our versatile platform utilizes a ferromagnetic substrate that stabilizes the organic magnetic moments against thermal and quantum fluctuations, while being fully compatible with on-surface synthesis of the rapidly growing class of nanographenes.

On-Surface Synthesis and Characterization of a High-Spin Aza-[5]-Triangulene.

Triangulenes are a class of open-shell triangular graphene flakes with total spin increasing with their size. In the last years, on-surface-synthesis strategies have permitted fabricating and engineering triangulenes of various sizes and structures with atomic precision. However, direct proof of the increasing total spin with their size remains elusive. In this work, we report the combined in-solution and on-surface synthesis of a large nitrogen-doped triangulene (aza-[5]-triangulene) on a Au(111) surface, and the detection of its high-spin ground state. Bond-resolved scanning tunneling microscopy images uncovered radical states distributed along the zigzag edges, which were detected as weak zero-bias resonances in scanning tunneling spectra. These spectral features reveal the partial Kondo screening of a high-spin state. Through a combination of several simulation tools, we find that the observed distribution of radical states is explained by a quintet ground state (S=2), instead of the quartet state (S=3/2) expected for the neutral species. This confirms that electron transfer to the metal substrate raises the spin of the ground state. We further provide a qualitative description of the change of (anti)aromaticity introduced by N-substitution, and its role in the charge stabilization on a surface, resulting in an S=2 aza-triangulene on Au(111).

Inhibition of Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily in Bacterial Pathogens.

Bacterial pathogens resistant to multiple structurally distinct antimicrobial agents are causative agents of infectious disease, and they thus constitute a serious concern for public health. Of the various bacterial mechanisms for antimicrobial resistance, active efflux is a well-known system that extrudes clinically relevant antimicrobial agents, rendering specific pathogens recalcitrant to the growth-inhibitory effects of multiple drugs. In particular, multidrug efflux pump members of the major facilitator superfamily constitute central resistance systems in bacterial pathogens. This review article addresses the recent efforts to modulate these antimicrobial efflux transporters from a molecular perspective. Such investigations can potentially restore the clinical efficacy of infectious disease chemotherapy.

Molecular Bridge Engineering for Tuning Quantum Electronic Transport and Anisotropy in Nanoporous Graphene.

Recent advances on surface-assisted synthesis have demonstrated that arrays of nanometer wide graphene nanoribbons can be laterally coupled with atomic precision to give rise to a highly anisotropic nanoporous graphene structure. Electronically, this graphene nanoarchitecture can be conceived as a set of weakly coupled semiconducting 1D nanochannels with electron propagation characterized by substantial interchannel quantum interferences. Here, we report the synthesis of a new nanoporous graphene structure where the interribbon electronic coupling can be controlled by the different degrees of freedom provided by phenylene bridges that couple the conducting channels. This versatility arises from the multiplicity of phenylene cross-coupling configurations, which provides a robust chemical knob, and from the interphenyl twist angle that acts as a fine-tunable knob. The twist angle is significantly altered by the interaction with the substrate, as confirmed by a combined bond-resolved scanning tunneling microscopy (STM) and ab initio analysis, and should accordingly be addressable by other external stimuli. Electron propagation simulations demonstrate the capability of either switching on/off or modulating the interribbon coupling by the corresponding use of the chemical or the conformational knob. Molecular bridges therefore emerge as efficient tools to engineer quantum transport and anisotropy in carbon-based 2D nanoarchitectures.

Methemoglobinemia Secondary to Inhalation of Automobile Emissions with Suicide Motivations.

BACKGROUND: Methemoglobinemia (MetHb) is a rare and potentially severe dyshemoglobinemia that can be induced by exposure to oxidizing agents, decreasing the functional capacity of the hemoglobin molecule to transport and release oxygen into the tissues. MetHb can originate from gases with oxidizing capacity generated by internal combustion engines, although since the universalization of catalyst converters in automobiles, a tiny proportion of MetHb poisoning is due to exposure to engine gases and fumes. Within this group, only two cases due to suicidal motivations have been reported in the last 30 years. CASE PRESENTATION: Here, we expose the case of a patient with MetHb levels of 25.2% (normal 0-1.5%) who with suicidal motivations had attached and locked a hose to the exhaust pipe of her vehicle with electrical tape, becoming exposed to a sustained concentration of the vehicle's exhaust. Upon her arrival at the emergency department, the presence of generalized greyish cyanosis with alterations of the sensorium, dissociation between saturation measured by arterial blood gas analysis and pulse oximetry (98% vs. 85%), no response to high-flow oxygen therapy, and an excellent response to intravenous methylene blue treatment were highlighted. CONCLUSIONS: This report illustrates an original case of acute toxic acquired MetHb due to inhalation of oxidizing substances originating from the bad ignition of an internal combustion engine. When evaluating a patient with suspected gas intoxication, we usually consider poisoning by the most common toxins, such as carbon monoxide or cyanide. In this context, we propose an algorithm to assist in the suspicion of this entity in patients with cyanosis in the emergency department. MetHb poisoning should be suspected, and urgent co-oximetry should be requested when there is no congruence between cyanosis intensity and oxygen saturation measured by pulse oximetry, if there is discordance between the results of oxygen saturation measured by arterial blood gas and pulse oximeter, and if there is no response to oxygen treatment. This algorithm could be useful to not delay diagnosis, improve prognosis, and limit potential sequelae.

The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE Pathogen Staphylococcus aureus.

The ESKAPEE bacterial pathogen Staphylococcus aureus has posed a serious public health concern for centuries. Throughout its evolutionary course, S. aureus has developed strains with resistance to antimicrobial agents. The bacterial pathogen has acquired multidrug resistance, causing, in many cases, untreatable infectious diseases and raising serious public safety and healthcare concerns. Amongst the various mechanisms for antimicrobial resistance, integral membrane proteins that serve as secondary active transporters from the major facilitator superfamily constitute a chief system of multidrug resistance. These MFS transporters actively export structurally different antimicrobial agents from the cells of S. aureus. This review article discusses the S. aureus-specific MFS multidrug efflux pump systems from a molecular mechanistic perspective, paying particular attention to structure-function relationships, modulation of antimicrobial resistance mediated by MFS drug efflux pumps, and direction for future investigation.

An intergenerational programme delays health impairment in nursing home residents: the Duplo project.

PURPOSE: To analyse whether an intergenerational programme in which students interacted with institutionalised older persons had any impact on the older persons' functional status. METHODS: Each academic year, a group of older adults living in nursing homes were divided into two arms. For the next four months, the first group received daily visits from a group of students during which they followed a pre-established activity plan, whilst the other arm proceeded with their normal activity. After 4 months, the groups crossed over, and the second arm received the student visits, whilst the first group returned to their normal activity. A battery of tests was performed at inception, crossover and the end of the second period. The tests explored mobility (Timed Up-and-Go), cognition (Mini-Mental Examination), executive function (Frontal Assessment Battery) and mood (Geriatric Depression Scale). A dichotomous aggregate "significant impairment" variable was deemed to be present when there was at least a 20% loss of function (compared to the value at the beginning of the period) in any of the aforementioned tests. RESULTS: The study included 289 older adults who visited with 91 students. Subjects in the active phase had a lower incidence of significant impairment than those in the control phase (O.R. 0.90, p < 0.01). There were no significant differences in the individual variables. CONCLUSION: An intergenerational project with students visiting older adults in nursing homes had a protective effect, delaying functional decay in older adults.

Circumventing the stability problems of graphene nanoribbon zigzag edges.

Carbon nanostructures with zigzag edges exhibit unique properties-such as localized electronic states and spins-with exciting potential applications. Such nanostructures however are generally synthesized under vacuum because their zigzag edges are unstable under ambient conditions: a barrier that must be surmounted to achieve their scalable integration into devices for practical purposes. Here we show two chemical protection/deprotection strategies, demonstrated on labile, air-sensitive chiral graphene nanoribbons. Upon hydrogenation, the chiral graphene nanoribbons survive exposure to air, after which they are easily converted back to their original structure by annealing. We also approach the problem from another angle by synthesizing a form of the chiral graphene nanoribbons that is functionalized with ketone side groups. This oxidized form is chemically stable and can be converted to the pristine hydrocarbon form by hydrogenation and annealing. In both cases, the deprotected chiral graphene nanoribbons regain electronic properties similar to those of the pristine nanoribbons. We believe both approaches may be extended to other graphene nanoribbons and carbon-based nanostructures.

Lactate biosensing based on covalent immobilization of lactate oxidase onto chevron-like graphene nanoribbons via diazotization-coupling reaction.

We have designed and prepared an electrochemical biosensor for lactate determination. Through a diazotation process, the enzyme lactate oxidase (LOx) is anchored onto chevron-like graphene nanoribbons (GNR), previously synthesized by a solution-based chemical route, and used as modifiers of glassy carbon electrodes. In a first step, we have performed the grafting of a 4-carboxyphenyl film, by electrochemical reduction of the corresponding 4-carboxyphenyl diazonium salt, on the GNR-modified electrode surface. In this way, the carboxylic groups are exposed to the solution, enabling the covalent immobilization of the enzyme through the formation of an amide bond between these carboxylic groups and the amine groups of the enzyme. The biosensor design was optimized through the morphological and electrochemical characterization of each construction step by atomic force microscopy, scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy.The cyclic voltammetric response of the biosensor in a solution of hydroxymethylferrocene in presence of l-lactate evidenced a clear electrocatalytic effect powered by the specific design of the biosensing platform with LOx covalently attached to the GNR layer. From the calibration procedures employed for l-lactate determination, a linear concentration range of 3.4 · 10-5- 2.8 · 10-4 M and a detection limit of 11 µM were obtained, with relative errors and relative standard deviations less than 6.0% and 8.4%, respectively. The applicability of the biosensor was tested by determining lactate in apple juices, leading to results that are in good agreement with those obtained with a well-established enzymatic spectrophotometric assay kit.

Discriminating Bacterial Infection from Other Causes of Fever Using Body Temperature Entropy Analysis.

Body temperature is usually employed in clinical practice by strict binary thresholding, aiming to classify patients as having fever or not. In the last years, other approaches based on the continuous analysis of body temperature time series have emerged. These are not only based on absolute thresholds but also on patterns and temporal dynamics of these time series, thus providing promising tools for early diagnosis. The present study applies three time series entropy calculation methods (Slope Entropy, Approximate Entropy, and Sample Entropy) to body temperature records of patients with bacterial infections and other causes of fever in search of possible differences that could be exploited for automatic classification. In the comparative analysis, Slope Entropy proved to be a stable and robust method that could bring higher sensitivity to the realm of entropy tools applied in this context of clinical thermometry. This method was able to find statistically significant differences between the two classes analyzed in all experiments, with sensitivity and specificity above 70% in most cases.

High-Sensitivity Troponin T: A Potential Safety Predictive Biomarker for Discharge from the Emergency Department of Patients with Confirmed Influenza.

The purpose of the study was to analyze the relationship between the high-sensitivity troponin T levels in patients with confirmed influenza virus infection and its severity determined by mortality during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow us to a safe discharge from the emergency department. An analytical retrospective observational study was designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed until the resolution of the clinical picture, and the frequency of mortality is analyzed. We included patients ≥ 16 years old with confirmed influenza virus infection and determination of high-sensitivity troponin T. One hundred twenty-eight patients were included (96.9% survivors, 3.1% deceased). Mean and median blood levels of high-sensitivity troponin T of survivors were 26.2 ± 58.3 ng/L and 14.5 ng/L (IQR 16 ng/L), respectively, and were statistically different when compared with those of the deceased patients, 120.5 ± 170.1 ng/L and 40.5 ng/L (IQR 266.5 ng/L), respectively, p = 0.012. The Youden index using mortality as the reference method was 0.76, and the cut-off value associated with this index was 24 ng/L (sensitivity 100%, specificity 76%, NPV 100%, PPV 4%) with AUC of 88,8% (95% CI: 79.8−92.2%), p < 0.001. We conclude that high-sensitivity troponin T levels in confirmed virus influenza infection are a good predictor of mortality in our population, and this predictor is useful for safely discharging patients from the emergency department.

Spreading a Strategy to Prevent Suicide After Psychiatric Hospitalization: Results of a Quality Improvement Spread Initiative.

BACKGROUND: Suicide after psychiatric hospitalization is a major concern. Poor treatment engagement may contribute to risk. The World Health Organization Brief Intervention and Contact (BIC) Program is an evidence-based practice shown to prevent suicide after psychiatric discharge in international trials. There have been no efforts to implement BIC into routine practice in US populations. METHODS: The authors conducted a 12-month quality improvement (QI) collaborative at six US Department of Veterans Affairs (VA) medical centers serving a large rural population. Sites had low to moderate performance on a VA quality measure of mental health postdischarge care; a measure assessing the proportion of discharged patients who achieve the required number of visits ≤ 30 days. Sites received programmatic support to implement BIC locally. Implementation was assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. RESULTS: Overall, teams had high participation in programmatic activities and enrolled 85% of eligible patients that they approached. Among 70 enrolled patients, 81.4% achieved the VA quality measure of mental health postdischarge care, suggesting good treatment engagement. On average, patients rated BIC as excellent. Team members agreed that BIC was easy to use, implementable, possible, and doable. Factors facilitating implementation included standardized operating procedures to standardize processes. Barriers included insufficient staffing and loss to follow-up. Most sites plan to continue to enroll patients and to expand BIC to other areas. CONCLUSION: A QI collaborative can facilitate implementation of BIC in six VA facilities that provide inpatient psychiatric treatment. BIC may appeal to patients and providers and may improve treatment engagement.