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.

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.

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.

The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally (n = 17) or parenterally (n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03), nasal, and pharyngeal (P < 0.01) microbiotas. The appearance of resistant strains was observed only in enterococci from the fecal microbiota between the 7th and 21st days of treatment in four patients (14.3%). The resistance was mainly due for the first time to the mutation G2447T in the 23S rRNA gene. No pharmacokinetic parameters were significantly different between the patients, regardless of the appearance of resistance. The emergence of linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas.

Ethical Dilemnia of the Therapeutic Decisions in the Care of the Severe Chronic Anorexia Nervosa: About a Case.

When caring for of patients suffering from severe anorexia, medical teams may feel deprived in the face of the ambivalent behavior of some of these patients who accept medical care but refuse nutrition. We present here the case of a woman suffering from severe chronic anorexia with a state of morbid malnutrition, which presented the ethical question of how to deal with this unreasonable attitude. These extreme cases raise several questions regarding avoiding malfeasance and when to provide palliative care in a management of psychiatric pathology.

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.

Bayesian modeling of Clostridium perfringens growth in beef-in-sauce products.

Models on Clostridium perfringens growth which have been published to date have all been deterministic. A probabilistic model describing growth under non-isothermal conditions was thus proposed for predicting C. perfringens growth in beef-in-sauce products cooked and distributed in a French hospital. Model parameters were estimated from different types of data from various studies. A Bayesian approach was proposed to model the overall uncertainty regarding parameters and potential variability on the 'work to be done' (h(0)) during the germination, outgrowth and lag phase. Three models which differed according to their description of this parameter h(0) were tested. The model with inter-curve variability on h(0) was found to be the best one, on the basis of goodness-of-fit assessment and validation with literature data on results obtained under non-isothermal conditions. This model was used in two-dimensional Monte Carlo simulations to predict C. perfringens growth throughout the preparation of beef-in-sauce products, using temperature profiles recorded in a hospital kitchen. The median predicted growth was 7.8×10(-2) log(10) cfu·g(-1) (95% credibility interval [2.4×10(-2), 0.8]) despite the fact that for more than 50% of the registered temperature profiles cooling steps were longer than those required by French regulations.

Rapid evolution of Wolbachia density in insecticide resistant Culex pipiens.

The maternally inherited symbiotic Wolbachia have been previously shown to have much greater densities in insecticide-resistant Culex pipiens mosquitoes than in insecticide-susceptible individuals. These high densities were shown to be at least partially responsible for the costs related to insecticide resistance in this species. We report here the rapid evolution, on the order of 50 generations, of bacterial densities both in laboratory and field populations. Along with other recently published studies, this report shows that Wolbachia-host interactions are very dynamic.

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.

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.

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).

[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.

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.

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.

Investigations of the steric effect on electrochemical transduction in a quinone-based DNA sensor.

Electrochemical biosensors for DNA hybridization are receiving increasing interest. A key point for their efficiency is to obtain a high signal level for low DNA concentration. This implies the design of an efficient transducing surface. Conducting polymers are interesting for this purpose but the great majority of conducting polymer-based electrodes present a signal decrease upon hybridization (a "signal-off" behavior), which impedes their response and makes them sensitive to false positive ones. The sensor described here presents a "signal-on" behavior, due to the use of a quinone group as the transducing agent. The specific aim of this work is to study the steric effect on transduction. To this end, the electrochemical response was monitored versus the DNA target length, for a constant DNA probe length. The results indicate that the current depends on the length of the double strand. A model which can explain the electrochemical behavior takes into account the steric hindrance of the ODN strands.

[Management of 90 patients presenting with suspected severe acute respiratory syndrome. Experience of a collaboration between epidemiologists and clinicians facing an emerging infectious disease health alert]. / Prise en charge de 90 patients suspects de syndrome respiratoire aigu sévère. Expérience d'une collaboration épidémioclinique en situation d'alerte sanitaire liée à une infection émergente.

OBJECTIVE: The characteristics of patients with a suspected SARS hospitalized in a Paris hospital were studied to analyze the hypothetic differences between epidemiologic and clinical teams in the management of an epidemic emerging disease, and to gather experience for the management of the next outbreak. STUDY DESIGN: All 90 patients hospitalized between March 16 and April 30, 2003, were included. Epidemiological and clinical data were shared with the French National Institute for Health. Cases were classified according to both the official definition ("possible", "probable", "excluded") and a local one, adapted from the official definition but including an additional level of suspicion ("equivocal"), intermediate between "possible" and "excluded". RESULTS: The initial assessment was different in 39% of the cases (n=35), according to epidemiological (n=24) or clinical (n=11) elements. The final assessment diverged in 54% of the cases (n=47). All patients were officially considered as "excluded" for epidemiologists, while 47 remained as "possible" or "equivocal" cases of SARS according to the clinicians. CONCLUSION: The risk assessment was different in almost 40% of the cases, with no impact on epidemic diffusion or hospital-borne exposure as no probable case of SARS was diagnosed among these patients or their households. The confrontation of these different but complementary points of view will thus enrich the interdisciplinary management of eventual future outbreaks.

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.