Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study.

BACKGROUND: Shigella spp have been associated with community-wide outbreaks in urban settings. We analysed a sustained shigellosis outbreak in Seattle, WA, USA, to understand its origins and mechanisms of antimicrobial resistance, define ongoing transmission patterns, and optimise strategies for treatment and infection control. METHODS: We did a retrospective study of all Shigella isolates identified from stool samples at the clinical laboratories at Harborview Medical Center and University of Washington Medical Center (Seattle, WA, USA) from May 1, 2017, to Feb 28, 2022. We characterised isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing. Demographic characteristics and clinical outcomes of the patients were retrospectively examined. FINDINGS: 171 cases of shigellosis were included. 78 (46%) patients were men who have sex with men (MSM), and 88 (52%) were people experiencing homelessness (PEH). Although 84 (51%) isolates were multidrug resistant, 100 (70%) of 143 patients with data on antimicrobial therapy received appropriate empirical therapy. Phylogenomic analysis identified sequential outbreaks of multiple distinct lineages of Shigella flexneri and Shigella sonnei. Discrete clonal lineages (ten in S flexneri and nine in S sonnei) and resistance traits were responsible for infection in different at-risk populations (ie, MSM, PEH), enabling development of effective guidelines for empirical treatment. The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups. INTERPRETATION: An outbreak in Seattle was driven by parallel emergence of multidrug-resistant strains involving international transmission networks and domestic transmission between at-risk populations. Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection. FUNDING: None.

Self-Assembly of Nanoparticles from Evaporating Sessile Droplets: Fresh Look into the Role of Particle/Substrate Interaction.

We studied the dependence of solid deposit shape obtained by free drying of sessile drops on particle concentration and Derjaguin-Landau-Verwey-Overbeek (DLVO) particle/substrate interaction. In contrast to previous contributions using pH as a control parameter of interactions, we investigated an unprecedentedly wide range of concentrations and particle/substrate DLVO forces by modifying the nature of the substrate and particles as well as their size and surface chemistry, whereas long-distance repulsive interactions between particles were maintained for most of the drying time. Our main result is that the different shapes of deposits obtained by modifying the particle concentration are the same in the different regimes of concentration regardless of particle/substrate interaction in the studied range of DLVO forces and particle concentrations. The second result is that, contrary to expectations, the dominant morphology of dry patterns at low particle concentration always shows a dotlike pattern for all the studied systems.

Morphological Control of Linear Particle Deposits from the Drying of Inkjet-Printed Rivulets.

We studied the morphology of linear particle deposits obtained by inkjet printing of a silica nanoparticle suspension in drying conditions where contact line depinning occurs. We show that this evaporation mode can be obtained by adjusting the particle concentration in different solvents. For isolated drops, deposited manually or by inkjet printing, drying induces the formation of two concentric rings in which particles self-assemble into a monolayer. For fused drops, our main result is that stable rivulets could be formed by drop overlap leading, after drying, to the formation of three parallel lines composed of a self-assembled particle monolayer. The three lines are of homogeneous thickness with two very thin outer lines (∼1 µm width) and a wider central line (∼20 µm width). We reveal how the width of the resulting lines is influenced by drop spacing in a predictable manner for a large experimental window knowing the drop size.

Self-Assembly of Gold Nanoparticles with Oppositely Charged, Long, Linear Chains of Periodic Copolymers.

We studied the assembly of nanoparticles (NPs) with oppositely charged linear and periodic copolymers (CPs), alternating ionic and polar sequences, in the dilute range of polymer concentration. For the first time, we considered CPs displaying a contour length much higher than the gold NP (AuNP) perimeter. We assumed that such CPs will enable the collection of a finite number of NPs into linear nanostructures with a gain of colloidal stability and a better structural control compared to electrostatic complexes obtained with homopolyelectrolytes. As a case study, we synthesized anionic AuNPs and CPs consisting of alternated cationic poly-l-lysine (PLL) blocks and polar sequences of poly(ethylene glycol) (PEG). We showed that complexation of AuNPs with CPs is quite similar to that observed with homo PLL. In that respect, finite size nanometric clusters, of less than 30 NPs, are formed outside the electroneutrality domain and a fast phase separation occurs at the electroneutrality. Nevertheless, the presence of PEG blocks allowed us to highlight some specific effects. First, the global charge of the positively charged clusters was found to be always lower for CP-based clusters than for homo PLL with a dependence of the charge with the number and the mass of the PEG blocks. Second, in spite of this effect which should have promoted the formation of a dense structure, the fractal dimension characterizing the structure of the clusters in bulk was found to be always below 1.8. Finally, we showed that PEG blocks influence the interparticle distance by disfavoring plasmon delocalization when the clusters are dispersed in water and collapse around the NPs when the clusters are deposited on the substrate.

Diurnal variations of cloud and relative humidity profiles across the tropics.

Even though the diurnal cycle of solar forcing on the climate system is well defined, the diurnal evolutions of water vapor and clouds induced by the solar forcing are not yet established across the tropics. Here we combine recent satellite observations of clouds profiles and relative humidity profiles to document the diurnal variations of the water vapor and clouds vertical distributions over all the tropics in June-July-August. While the daily mean water vapor and cloud profiles are different between land and ocean, their diurnal variations with respect to their daily means exhibit similar features. Relative humidity profiles and optically thin cloud fraction profiles vary together which maximize during night-time in the entire troposphere and a minimize in day-time. The fraction of optically opaque clouds peak in the free troposphere in the early afternoon, transforms into a high altitude positive anomaly of optically thin clouds from nightfall to sunrise. In addition, land regions exhibit a daily low thin cloud positive anomaly, while oceanic regions exposed to subsidence air motions exhibit positive anomalies of opaque clouds in the lower atmosphere during the second half of the night, which grow until sunrise.

Peptide-modified electrolyte-gated organic field effect transistor. Application to Cu2+ detection.

This work proposes an approach for Cu2+ sensing in water which combines the selectivity of the Gly-Gly-His (GGH) peptide probe with the sensitivity of the electrolyte-gated organic field-effect transistor (EGOFET). The oligopeptide probe was immobilized onto the gate electrode of the transistor by electrooxidation of the primary amine of the glycine moiety. Cu2+ complexation by the grafted GGH was at first electrochemically evidenced, using cyclic and square wave voltammetries, then it was demonstrated that GGH-functionalized EGOFETs can transduce Cu2+ complexation through a significant threshold voltage shift and therefore a change in drain current. The limit of detection is ca. 10-12 M and the sensitivity in the linear range (10-12 - 10-8 M) is 1 mA dec-1 (drain current variations).

Triggering the Electrolyte-Gated Organic Field-Effect Transistor output characteristics through gate functionalization using diazonium chemistry: Application to biodetection of 2,4-dichlorophenoxyacetic acid.

We investigated an Electrolyte-Gated Organic Field-Effect transistor based on poly(N-alkyldiketopyrrolo-pyrrole dithienylthieno[3,2-b]thiophene) as organic semiconductor whose gate electrode was functionalized by electrografting a functional diazonium salt capable to bind an antibody specific to 2,4-dichlorophenoxyacetic acid (2,4-D), an herbicide well-known to be a soil and water pollutant. Molecular docking computations were performed to design the functional diazonium salt to rationalize the antibody capture on the gate surface. Sensing of 2,4-D was performed through a displacement immunoassay. The limit of detection was estimated at around 2.5 fM.

[From pediatric care to adult medicine: Transition of sickle cell patients, a French monocentric study]. / De la pédiatrie à la médecine adulte : transition des patients drépanocytaires, une étude monocentrique française.

Sickle cell disease, a hemoglobin disorder with autosomal recessive transmission, is one of the most common genetic diseases screened in France. Thanks to early management, 95% of sickle cell patients reach adulthood and require transition from pediatric care to adult care. Through a retrospective study of records from serious sickle cell patients over 17 years old, followed in the hematology-oncology pediatric unit of Reims University Hospital Center in France, we analyzed transition conditions, compared pediatric and adult management, and proposed a plan for transition care. As of 1 January 2016, out of 19 sickle cell patients meeting the inclusion criteria, 12 had made the transition from pediatric care to adult medicine. Among the transition group, the transition was proposed by the pediatrician in 92% of cases. The average age of transition was 19.4 years. The time between receiving the information and the last pediatric visit was 2.4 months. Seven out of the 12 patients were informed of their transition during the last pediatric visit. The age of the first adult visit was 20.3 years. There was no alternate or joint consultation. The treatments prescribed during the last pediatric visit were not modified during the first adult visit. The average number of hospitalizations per patient was 2.7 in pediatric care and 3.4 in adult care with a median value of 2 in both groups. Three out of 12 patients died, the average age of death being 26.7 years. Transition is an important milestone in chronic disease patients. More than age, the maturity of the patient must be taken into account. The transition to the adult structure requires early preparation in the teenage years and investment of the adolescent and his family as well as investment of pediatric and adult caregivers. This study points out the need to establish a transition plan within our hospital in collaboration with adult physicians. Continuity of care is necessary to increase the quality of managing patients and cannot be done without a close relationship between pediatric specialists and adult physicians.

Mixed-methods development of a new patient-reported outcome instrument for chronic low back pain: part 1-the Patient Assessment for Low Back Pain - Symptoms (PAL-S).

We describe the mixed-methods (qualitative and quantitative) development and preliminary validation of the Patient Assessment for Low Back Pain-Symptoms (PAL-S), a patient-reported outcome measure for use in chronic low back pain (cLBP) clinical trials. Qualitative methods (concept elicitation and cognitive interviews) were used to identify and refine symptom concepts and quantitative methods (classical test theory and Rasch measurement theory) were used to evaluate item- and scale-level performance of the measure using an iterative approach. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and interview-based assessment of paper-to-electronic mode equivalence (N = 8). A web-based sample of patients with self-reported cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and a physician-diagnosed cohort of patients with cLBP (N = 45) participated in preliminary validation of the measure. The PAL-S contained 14 items describing symptoms (overall pain, sharp, prickling, sensitive, tender, radiating, shocking, shooting, burning, squeezing, muscle spasms, throbbing, aching, and stiffness). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test-retest reproducibility was acceptable (intraclass correlation coefficient 0.81 [95% confidence interval, 0.61-0.91]). Convergent validity was demonstrated with total score and MOS-36 Bodily Pain (Pearson correlation -0.79), Neuropathic Pain Symptom Inventory (0.73), Roland-Morris Disability Questionnaire (0.67), and MOS-36 Physical Functioning (-0.65). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Respondent interpretation of paper and electronic administration modes was equivalent. The PAL-S has demonstrated content validity and is potentially useful to assess treatment benefit in cLBP clinical trials.

Enzyme-less electrochemical displacement heterogeneous immunosensor for diclofenac detection.

We describe an electrochemical immunosensor based on functionalization of a working electrode by electrografting two functional diazonium salts. The first one is a molecular probe, diclofenac, coupled with an arylamine onto which a specific antibody is immobilized by affinity interactions; the second is a redox probe (a quinone) also coupled with an arylamine, able to transduce the hapten-antibody association into a change in electroactivity. The steric hindrance induced by the antibody leads to a current decrease upon binding of the antibody on the grafted molecular probe; conversely, when diclofenac is present in solution, a displacement equilibrium occurs between the target diffusing into the solution and the grafted probe. This leads to dissociation of the antibody from the electrode surface, event which is transduced into a current increase ("signal-on" detection). The detection limit is ca. 20 fM, corresponding to 6pgL-1 diclofenac, which is competitive compared to other label-free immunosensors. We demonstrate that the sensor is selective and is able to quantify diclofenac in tap water.

Assessment of Patient-Reported Outcome Instruments to Assess Chronic Low Back Pain.

Objective: To identify patient-reported outcome (PRO) instruments that assess chronic low back pain (cLBP) symptoms (specifically pain qualities) and/or impacts for potential use in cLBP clinical trials to demonstrate treatment benefit and support labeling claims. Design: Literature review of existing PRO measures. Methods: Publications detailing existing PRO measures for cLBP were identified, reviewed, and summarized. As recommended by the US Food & Drug Administration (FDA) PRO development guidance, standard measurement characteristics were reviewed, including development history, psychometric properties (validity and reliability), ability to detect change, and interpretation of observed changes. Results: Thirteen instruments were selected and reviewed: Low Back Pain Bothersomeness Scale, Neuropathic Pain Symptom Inventory, PainDETECT, Pain Quality Assessment Scale Revised, Revised Short Form McGill Pain Questionnaire, Low Back Pain Impact Questionnaire, Oswestry Disability Index, Pain Disability Index, Roland-Morris Disability Questionnaire, Brief Pain Inventory and Brief Pain Inventory Short Form, Musculoskeletal Outcomes Data Evaluation and Management System Spine Module, Orebro Musculoskeletal Pain Questionnaire, and the West Haven-Yale Multidimensional Pain Inventory Interference Scale. The instruments varied in the aspects of pain and/or impacts that they assessed, and none of the instruments fulfilled all criteria for use in clinical trials to support labeling claims based on recommendations outlined in the FDA PRO guidance. Conclusions: There is an unmet need for a validated PRO instrument to evaluate cLBP-related symptoms and impacts for use in clinical trials.

A Retrospective Study To Determine Patients' Satisfaction With Fixed Dental Prostheses Provided During The Period 2008 ­ 2012 at The School of Dentistry In Trinidad

Introduction : The School of Dentistry undertakes the training of dental students, where they provide fixed dental prostheses such as crowns bridges and onlays to patients of the dental polyclinic. The aim of this study was to determine the patient satisfaction with their ixed prostheses and the quantity of remakes at the School of Dentistry polyclinic during the period 2008-2012. Methods : The lab records of ixed prosthetic work during the period 2008-2012 were analyzed. Patients who received treatment during this period were contacted via telephone for a structured interview via a questionnaire. Results : Ninety-six (96) patients were contacted via telephone and 72% of patients were female. Fifty-six (56) crowns and onlays, 22 conventional bridges and 18 resin-retained bridges were provided for patients. Ninety-six (96%) of patients were satisied with the aesthetics (appearance) of their prosthesis immediately after itting and 90.7 % were still satisied with the appearance at the time of interview. 79.2% of prostheses were still in place at the time of interview but patients reported that 18% of crowns failed, 22.7% of conventional bridges and 27.8% of resin-retained bridges had failed. Fifteen (15%) of the ixed prostheses were remade. However, the majority of patients (99 %) were overall satisied with their services at the School of Dentistry in Trinidad. Conclusion : Patients are generally satisied with the ixed prosthetic work delivered at the School of Dentistry polyclinic and highly satisied with the services provided. The amount of remakes whilst small can be reduced with more stringent quality assurance measures.

Grafting of a peptide probe for Prostate-Specific Antigen detection using diazonium electroreduction and click chemistry.

The main objective of this work was to validate a label-free electrochemical method of protein detection using peptides as capture probes. As a proof-of-concept, we used a 7 amino acids sequence (HSSKLQL) specific for Prostate Specific Antigen. We investigated various electrografting conditions of two anilines (2-[(4-aminophenyl)sulfanyl]-8-hydroxy-1,4-naphthoquinone and 4-azidoaniline) further converted in situ into their corresponding diazonium salts on glassy carbon electrodes. It was demonstrated that the best method to obtain a mixed layer is the simultaneous electroreduction of the two diazonium salts. 4-azidoaniline was used to covalently immobilize the ethynyl-functionalized peptide probe by click coupling, and the hydroxynaphthoquinone derivative plays the role of electrochemical transducer of the peptide-protein recognition. The proteolytic activity of PSA towards a small peptide substrate carrying streptavidin at its distal end was also investigated to design an original sensing architecture leading to a reagentless, label free, and "signal-on" PSA sensor. Without optimization, the limit of quantification can be estimated in the nM to pM range.

Scedosporium apiospermum Otitis Complicated by a Temporomandibular Arthritis: A Case Report and Mini-Review.

Scedosporium apiospermum is an ubiquitous fungus responsible for various infections in immunocompromised and immunocompetent patients. Ear infections are infrequent. We report an exceptional case of S. apiospermum external otitis complicated by temporomandibular joint arthritis. After 6 months of antibiotherapy, diagnosis was established by mycological analysis of external auditory canal and infratemporal fossae needle sampling. A satisfactory outcome was obtained after 2 months of voriconazole alone. We have reviewed 15 cases of S. apiospermum otitis. Seven of these patients were immunocompromised. Most common clinical presentation included a chronic external otitis lasting months or years before complication stage. Most common clinical features included recurrent unilateral otalgia (11/15) and purulent otorrhea (13/15). Diagnosis was often made at later stage (12/15) with local extension to bones and/or soft tissues (9/15) or cerebral lethal dissemination (3/15).The extremely low incidence of S. apiospermum otomycosis and its non-specific presentation results in a frequent diagnosis delay. A mycological investigation should be performed in case of persistent external otitis and/or osteolysis despite prolonged antibiotic treatment to prevent further extension of the disease.

General approach for electrochemical detection of persistent pharmaceutical micropollutants: Application to acetaminophen.

We propose in this work a general and versatile methodology for electrochemical monitoring of persistent pharmaceutical micropollutants. The system presented is based on an electroactive and electropolymerized hapten (mimetic molecule of the pollutant to be detected) and a specific antibody that competitively binds either the hapten or the pollutant. The current delivered by the device depends on this competitive equilibrium and therefore on the pollutant's concentration. The determination of the pharmaceutical product operates within minutes, using square wave voltammetry without labeling or addition of a reactant in solution; the competitive hapten/antibody transduction produces a "signal-on" (a current increase). Applied to acetaminophen, this electrochemical immunosensor presents a very low detection limit of ca. 10 pM, (S/N=3) and a very high selectivity towards structural analogs (aspirin, BPA, and piperazine) even in a mixture.

Label-free electrochemical detection of prostate-specific antigen based on nucleic acid aptamer.

We report a label-free aptasensor to make direct detection of prostate specific antigen (PSA, a biomarker of prostate cancer) using a quinone-containing conducting copolymer acting as redox transducer and grafting matrix for immobilization of the short aptamer strands. It is shown that capture of PSA generates a current decrease (signal-off) measured by Square Wave Voltammetry. This current decrease is specific for PSA above a limit of quantification in the ng mL(-1) range. The change in current is used to determine the PSA-aptamer dissociation constant K(D), of ca. 2.6 nM. To consolidate the proof of concept, a heterogeneous competitive exchange with a complementary DNA strand which breaks PSA-aptamer interactions is studied. This double-check followed by a current increase provides full assurance of a perfectly specific recognition.

[Post-traumatic mucormycosis due to Lichtheimia corymbifera: three case reports]. / Mucormycoses post-traumatiques à Lichtheimia corymbifera: à propos de 3 cas.

We report 3 cases of post-traumatic cutaneous mucormycosis caused by Lichtheimia corymbifera, two of them occurring after a farm working accident. Management of post-traumatic mucormycoses consists of a wide excision of the infected tissue, combined with immediate antifungal therapy. Liposomal amphotericin B is the recommended first line treatment. Few studies have evaluated the efficacy of posaconazole. All 3 patients received a surgical debridement and liposomal amphotericin B, which was followed by posaconazole in 2 cases. The duration of the antifungal treatment is not yet well defined. All three patients received a treatment of five weeks with a favorable outcome.