Conformation changes in human hair keratin observed using confocal Raman spectroscopy after active ingredient application.

OBJECTIVE: In hair care cosmetic products' evaluation, one commonly used method is to evaluate the hair appearance as a gold standard in order to determine the effect of an active ingredient on the final state of the hair via visual appreciation. Although other techniques have been proposed for a direct analysis of the hair fibres, they give only surface or structural information, without any accurate molecular information. A different approach based on confocal Raman spectroscopy has been proposed for tracking in situ the molecular change in the keratin directly in the human hair fibres. It presents a high molecular specificity to detect chemical interactions between molecules and can provide molecular information at various depths at the cortex and cuticle levels. METHODS: To evaluate the potential of confocal Raman spectroscopy in testing the efficiency of cosmetic ingredients on keratin structure, we undertook a pilot study on the effectiveness of a smoothing shampoo on natural human hair, by analysing α-helix and ß-sheet spectral markers in the Amide I band and spectral markers specific to the cystin sulfur content. RESULTS: We confirmed that an active proved to be effective on a gold standard decreases α-helix keratin conformation and promotes ß-sheet keratin conformation in the hair fibres. We also showed that treatment with the effective active decreases the intensity of covalent disulfide (S-S at 510 cm-1 ) cross-linking bands of cysteine. These data confirm that the effective active also acts on the tertiary structure of keratin. CONCLUSION: From these experiments, we concluded that the effective active has a smoothing effect on the human hair fibres by acting on α-helix and ß-sheet keratin conformation and on the tertiary structure of keratin. Based on these results, confocal Raman spectroscopy can be considered a powerful technique for investigating the influence of hair cosmetic ingredients on keratin structure in human hair fibres. Moreover, this analytical technique has the advantage of being non-destructive and label free; in addition, it does not require sample extraction or purification and it can be applied routinely in cosmetic laboratories.

OBJECTIF: Dans l'évaluation des produits cosmétiques pour le soin des cheveux, une méthode communément utilisée consiste à évaluer l'aspect des cheveux afin de déterminer l'effet d'un principe actif sur l'état final des cheveux via l'appréciation visuelle. Bien que d'autres techniques ont été proposées pour une analyse directe de la fibre capillaire, elles ne donnent que des informations de surface ou de structure, sans aucune information moléculaire précise. Une approche différente par la spectroscopie confocale Raman a été proposée pour le suivi in situ du changement moléculaire de la kératine directement dans les fibres de cheveux humains. Il présente une grande spécificité moléculaire, détecter les interactions chimiques entre les molécules et peut fournir des informations moléculaires à différents niveaux de profondeur du cortex et de la cuticule. MÉTHODES: Afin d'évaluer le potentiel de la spectroscopie Raman confocale pour tester l'efficacité des ingrédients cosmétiques sur la structure de la kératine, nous avons entrepris une étude pilote sur l'efficacité d'un shampooing lissant sur cheveux naturels, en analysant les marqueurs spectraux de l'hélice α et du feuillet ß dans la bande Amide I et les marqueurs spectraux spécifiques au contenu en sulfure-cystine. RÉSULTATS: Nous avons confirmé qu'un actif s'avérant efficace sur un gold standard diminue la conformation de la kératine en hélice α et favorise la conformation de la kératine en feuillet ß dans les fibres des cheveux. Nous avons également montré que le traitement avec l'actif efficace diminue l'intensité des bandes de cystéine réticulant sous forme de ponts disulfures covalents (S - S à 510 cm-1). Ces données confirment que l'actif efficace agit également sur la structure tertiaire de la kératine. CONCLUSION: À partir de ces expériences, nous avons conclu que l'actif efficace a un effet lissant sur les fibres du cheveu humain en agissant sur la conformation hélice α et feuillet ß de la kératine et sur la structure tertiaire de la kératine. Sur la base de ces résultats, la spectroscopie confocale Raman peut être considérée comme une technique puissante pour étudier l'influence des ingrédients cosmétiques sur la structure de la kératine dans les fibres de cheveux. De plus, cette technique analytique a l'avantage d'être non destructive et ne nécessite pas de marquage; de plus, elle ne nécessite pas d'extraction ou de purification des échantillons et peut être appliquée en routine dans les laboratoires de cosmétiques.

[Does the delay from prostate biopsy to radical prostatectomy influence the risk of biochemical recurrence?] / Le delai entre biopsies de prostate et prostatectomie radicale influence-t-il le risque de recidive ?

INTRODUCTION: The influence of the delay between prostate biopsy and radical prostatectomy for patients with localized prostate cancer is controversial. The objective of this study was to establish a time limit between prostate biopsy and radical prostatectomy beyond which the risks of upgradging and biochemical recurrence (BCR) are increased. MATERIAL AND METHODS: Between January 2013 and January 2017, a retrospective analysis of the clinical, biological and histological data of 513 patients treated with radical prostatectomy for localized prostate cancer was performed in a single center. The primary endpoint was the assessment of the risk of BCR by the difference between post-biopsy USCF-CAPRA and post-surgical CAPRA-S scores. The secondary endpoint was the evaluation of the upgrading by the difference between the Gleason score on biopsy and on surgical specimen. The risks of BCR and upgrading were compared by Student test according to different delays between prostate biopsy and radical prostatectomy. The shortest delays for which a significant difference was found were reported. RESULTS: In this study, 513 patients were included. The median age at the time of the biopsy was 65 years (IQR: 60-69). The median preoperative PSA was 7.30ng/mL (IQR: 5.60-9.94). The median time between biopsy and surgery was 108 days (IQR: 86-141). For the entire cohort, the risk of BCR was significantly higher above a threshold of 90 days (P=0.039). No threshold was found for Gleason 6(3+3) patients. A 90-day threshold was found for Gleason 7(3+4) patients (P=0.038). Gleason patients≥8 had more upgrading beyond a 60-day threshold (P=0.040). CONCLUSION: Our study showed that after a 3 months delay, the risk of BCR was significantly higher for localized prostate cancer. It seemed possible to extend this period for low-risk patients, whereas it seemed necessary to keep it for intermediate-risks and to reduce it to 2 months for high-risks. LEVEL OF EVIDENCE: 4.

Control strategies against Campylobacter at the poultry production level: biosecurity measures, feed additives and vaccination.

Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union, and ranks second in the United States only behind salmonellosis. In Europe, there are about nine million cases of campylobacteriosis every year, making the disease a major public health issue. Human cases are mainly caused by the zoonotic pathogen Campylobacter jejuni. The main source of contamination is handling or consumption of poultry meat. Poultry constitutes the main reservoir of Campylobacter, substantial quantities of which are found in the intestines following rapid, intense colonization. Reducing Campylobacter levels in the poultry chain would decrease the incidence of human campylobacteriosis. As primary production is a crucial step in Campylobacter poultry contamination, controlling the infection at this level could impact the following links along the food chain (slaughter, retail and consumption). This review describes the control strategies implemented during the past few decades in primary poultry production, including the most recent studies. In fact, the implementation of biosecurity and hygiene measures is described, as well as the immune strategy with passive immunization and vaccination trials and the nutritional strategy with the administration of organic and fatty acids, essential oil and plant-derived compound, probiotics, bacteriocins and bacteriophages.

Predicting drug substances autoxidation.

PURPOSE: Chemical degradation and stability in formulation is a recurrent issue in pharmaceutical development of drugs. The objective of the present study was to develop an in silico risk assessment of active pharmaceutical ingredients (APIs) stability with respect to autoxidation. METHODS: The chemical degradation by autoxidation of a diverse series of APIs has been investigated with molecular modelling tools. A set of 45 organic compounds was used to test and validate the various computational settings. Aiming to devise a methodology that could reliably perform a risk assessment for potential sensibility to autoxidation, different types of APIs, known for their autoxidation history were inspected. To define the level of approximation needed, various density functional theory (DFT) functionals and settings were employed and their accuracy and speed were compared. RESULTS: The Local Density Approximation (LDA) gave the fastest results but with a substantial deviation (systematic over-estimation) to known experimental values. The Perdew-Burke-Ernzerhof (PBE) settings appeared to be a good compromise between speed and accuracy. CONCLUSIONS: The present methodology can now be confidently deployed in pharmaceutical development for systematic risk assessment of drug stability.

Bacteriophages: biosensing tools for multi-drug resistant pathogens.

Pathogen detection is of utmost importance in many sectors, such as in the food industry, environmental quality control, clinical diagnostics, bio-defence and counter-terrorism. Failure to appropriately, and specifically, detect pathogenic bacteria can lead to serious consequences, and may ultimately be lethal. Public safety, new legislation, recent outbreaks in food contamination, and the ever-increasing prevalence of multidrug-resistant infections have fostered a worldwide research effort targeting novel biosensing strategies. This review concerns phage-based analytical and biosensing methods targeted towards theranostic applications. We discuss and review phage-based assays, notably phage amplification, reporter phage, phage lysis, and bioluminescence assays for the detection of bacterial species, as well as phage-based biosensors, including optical (comprising SPR sensors and fiber optic assays), electrochemical (comprising amperometric, potentiometric, and impedimetric sensors), acoustic wave and magnetoelastic sensors.

Combined surface plasmon resonance and impedance spectroscopy systems for biosensing.

Combined surface plasmon resonance and electrochemical impedance spectroscopy (SP-EIS) biosensing systems have been developed. They use a sensor chip consisting of micrometer sized interdigitated metal electrodes (IDEs) which effectively act as a surface plasmon supporting structure. In addition, the interdigitated electrodes exhibit the properties of an optical dispersive grating reflecting white light into the diffraction orders. Direct surface plasmon spectral analysis is possible by using the first order of diffraction and has been used as a novel principle for a simplified optical set-up. SP-EIS is a promising technology for a variety of conductometric and SPR mono- and multisensing applications in portable or stationary platforms.

Iterative breakthrough invasive aspergillosis due to TR(34) /L98H azole-resistant Aspergillus fumigatus and Emericella sublata in a single hematopoietic stem cell transplant patient.

We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. This case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.

Prevalence and factors associated with overweight and obesity in dogs presenting to French university veterinary teaching hospitals during the COVID-19 pandemic.

Pet obesity is still a major health issue, which is considered an epidemic by some researchers. Prevention is one of the cornerstones of veterinary care, emphasizing the importance of proactive measures. Human lifestyle was affected during the COVID-19 pandemic, resulting in an increased overweight prevalence in the population. The prevalence of overweight and obesity in dogs during this period has been poorly explored. This study's objectives were to assess the percentage of the French dog population with overweight and obesity, compare the results with a study conducted before the COVID-19 pandemic, and investigate any potential changes in the risk factors. The study collected data through a survey completed by dog owners during their pets' vaccination visits at university veterinary hospitals of Maisons-Alfort (Paris) and Toulouse, in France, between 2020 and 2022. The veterinarian recorded the dog's weight and the body condition score using a 9-point scale. The study included a total of 309 dogs. Of these, 1.6 % were underweight, 63.1 % had an ideal body condition, and 35.3 % were overweight, including 2.3 % of all dogs classified as obese. During the pandemic, French dog diets shifted towards increased commercial food consumption and twice-daily feedings compared to a 2003 study. Factors positively associated with overweight were being female (OR = 3.55; 95 % CI: 1.65-8.01; P=0.002), being senior (OR=4.91; 95 % CI: 2.07-12.2; P<0.001) or geriatric (OR=5.81; 95 % CI: 2.04-17.0; P=0.001) and having an owner underestimating dog's body condition (OR=74.1; 95 % CI: 29.8-215; P<0.001). Recognizing the impact of owner perception enables early intervention strategies, such as educating owners during consultations and conducting teaching sessions at the clinic. This proactive approach could contribute to improved health outcomes and help prevent the onset of obesity-related issues in dogs. The new trends in dogs' diets may have global relevance due to the pandemic's widespread impact. Although no immediate impact on overweight is evident, ongoing research is crucial to understand the pandemic's long-term effects.

Discrimination of single base mismatched oligonucleotides related to the rpoB gene of Mycobacterium tuberculosis using a surface plasmon resonance biosensor.

Single base mismatched oligonucleotides related to the rpoB gene of Mycobacterium tuberculosis, the mutations of which cause drug resistance of the infectious agent, were detected and discriminated using a surface plasmon resonance biosensor system. Thiol-modified oligonucleotides of the selected sequence (the probe) and 1-mercapto-6-hexanol were immobilized on a gold sensor surface. Hybridization between immobilized probe P2 and perfectly matched target T2 as well as a single base mismatched target TN was investigated in buffer solutions of various stringencies. Discrimination of perfectly matched and single base mismatched targets is achieved due to a difference in the level of their hybridization with the immobilized probe depending on stringency of the buffer solution. In 0.5×SSC buffer solution (7.5 mM sodium citrate, pH 7, containing 75 mM NaCl), sensor response at T2 injection into the measuring sensor cell was 16 times that at TN injection. The experimental results on surface hybridization between the studied oligonucleotides demonstrated a good correlation with theoretical calculations of thermodynamic parameters of these interactions in the solution. The described approach could be proposed as a basis for creating a biosensor for real-time label-free diagnostics of drug-resistant tuberculosis.

Recognition memory and the medial temporal lobe: from monkey research to human pathology.

This review provides a historical overview of decades of research on recognition memory, the process that allows both humans and animals to tell familiar from novel items. The emphasis is put on how monkey research improved our understanding of the medial temporal lobe (MTL) role and how tasks designed for monkeys influenced research in humans. The story starts in the early 1950s. Back then, memory was not a fashionable scientific topic. It was viewed as a function of the whole brain and not of specialized brain areas. All that changed in 1957-1958 when Brenda Milner, a neuropsychologist from Montreal, described patient H.M. He forgot all events as he lived them despite a fully preserved intelligence. He had received a MTL resection to relieve epilepsy. H.M. (1926-2008) would become the most influential patient in brain science. Which structures among those included in H.M.'s large lesion were important for recognition memory could not be evaluated in humans. It was gradually understood only after the successful development of a monkey model of human amnesia by Mishkin in 1978. Selective lesions and two behavioral tasks, delayed nonmatching-to-sample and visual paired comparison, were used to distinguish the contribution of the hippocampus from that of adjacent cortical areas. Driven by findings in non-human primates, human research on recognition memory is now trying to solve the question of whether the different structures composing MTL contributes to familiarity and recollection, the two possible forms taken by recognition. We described in particular two French patients, FRG and JMG, whose deficits support the currently dominant model attributing to the perirhinal cortex a critical role in recognition memory. Research on recognition memory has implications for the clinician as it may help understanding the cognitive deficits observed in different diseases. An illustration of such approach, linking basic and applied research, is provided for Alzheimer's disease.

Integrated silicon-based nanoplasmonic sensor.

The concept of an integrated nanoplasmonic sensor implemented on a silicon substrate is presented. Developed experimental setup based on rotation of linearly polarized light provides intensity detection between two orthogonal polarizations of a He-Ne laser beam. This optical configuration yields to a sensitivity improvement and noise reduction, resulting in a resolution of 4x10(-5) Refractive Index Units. Proposed methodology is promising for the application in portable nanoplasmonic multisensing and imaging.

Role of near-field enhancement in plasmonic laser nanoablation using gold nanorods on a silicon substrate: comment.

In this comment, we argue that the conlusion made by Harrisson and Ben-Yakar [Opt. Express 18, 22556 (2010)], which states that nanoablation with plasmonic nanorods depends on the enhancement of the Poynting vector rather than the one of the square of the electric field, is incorrect and not necessarily needed to explain their experimental results.

Intensity based surface plasmon resonance sensor using a nanohole rectangular array.

We show high resolution measurements of a surface plasmon resonance (SPR) sensor based on a rectangular nanohole array in a metal film. This SPR setup uses balanced intensity detection between two orthogonal polarizations of a He-Ne laser beam, which allows for sensitivity improvement, noise reduction and rejection of any uncorrelated variation in the intensity signal. A bulk sensitivity resolution of 6.4 x 10(-6) RIU is demonstrated. The proposed methodology is promising for applications in portable nanoplasmonic multisensing and imaging.

Phase sensitive sensor on plasmonic nanograting structures.

In this paper, a concept of phase sensitive sensor based on plasmonic nanograting structures with normal incidence and transmission detection is presented. Performed theoretical modeling enables fabrication of nanostructures with optimal geometry for polarimetric measurements of the phase difference between s- and p- polarized light. High phase resolution of the optical setup (6*10(-3) deg.) allows detection of the bulk refractive index with sensitivity equal to 3.8*10(-6) RIU. Proposed technique presents a more efficient alternative to the conventional spectral interrogation method of nanoplasmonic-based sensing and could be used for multisensing or imaging applications.

Silver nanoparticle uptake in the human lung assessed through in-vitro and in-silico methods.

Silver nanoparticles (AgNP) are commonly used in medical, cosmetics, clothing, and industrial applications for their antibacterial and catalytic properties. As AgNP become more prevalent, the doses to which humans are exposed may increase and pose health risks, particularly through incidental inhalation. This exposure was evaluated through in-vitro methods simulating lung fluids and lung epithelium, and through computational fluid dynamics (CFD) methods of AgNP transport. A high-dose scenario simulated a short-term inhalation of 10 µg AgNP/m3, based on an exposure limit recommended by the National Institute of Occupational Safety and Health for the case of a health-care worker who handles AgNP-infused wound dressings, and regularly wears AgNP-imbedded clothing. Bioaccessibility tests were followed by a Parallel Artificial Membrane Permeability Assay (PAMPA) and supported by CFD models of the lung alveoli, membrane, pores, and blood capillaries. Results indicate that such exposure produces an average and maximum AgNP flux of approximately 4.7 × 10-21 and 6.5 × 10-19 mol m-2·s-1 through lung tissue, respectively, yielding a blood-silver accumulation of 0.46-64 mg per year, which may exceed the lowest adverse effect level of 25 mg for an adult male. Results from in-silico simulations were consistent with values estimated in vitro (within an order of magnitude), which suggest that CFD models may be used effectively to predict silver exposure from inhaled AgNP. Although the average short-term exposure concentrations are 3 orders of magnitude smaller than the reported threshold for mammalian cytotoxicity effects (observed at 5000 ppb), cumulative effects resulting from constant exposure to AgNP may pose risks to human health in the long-term, with predicted bioaccumulation reaching potential toxic effects after only five months of exposure, based on maximum flux.

Designing efficient zero calibration point for phase-sensitive surface plasmon resonance biosensing.

This work is related to the development of phase-sensitive methodologies in Surface Plasmon Resonance (SPR) biosensing. We take advantage of a specific angular dependence of phase of light, reflected under SPR geometry, on parameters of the SPR-supporting metal, and propose a polarimetry-based methodology to easily determine the optimal calibration zero point, corresponding to the maximal phase sensitivity. The proposed methodology can significantly facilitate the calibration of the system in field and multi-channel sensing, broaden the dynamic range, as well as contribute to the development of feedback loops.

Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing.

A novel polarimetry methodology for phase-sensitive measurements in single reflection geometry is proposed for applications in optical transduction-based biological sensing. The methodology uses altering step-like chopper-based mechanical phase modulation for orthogonal s- and p- polarizations of light reflected from the sensing interface and the extraction of phase information at different harmonics of the modulation. We show that even under a relatively simple experimental arrangement, the methodology provides the resolution of phase measurements as low as 0.007 deg. We also examine the proposed approach using Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries. For TIR geometry, the response appears to be strongly dependent on the prism material with the best values for high refractive index Si. The detection limit for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU) change. SPR geometry offers much stronger phase response due to a much sharper phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed methodology provides one of best sensitivities for phase-sensitive SPR devices. Advantages of the proposed method include high sensitivity, simplicity of experimental setup and noise immunity as a result of a high stability modulation.

Phase-sensitive silicon-based total internal reflection sensor.

A concept of phase-sensitive Si-based Total Internal Reflection bio- and chemical sensor is presented. The sensor uses the reflection of light from an internal edge of a Si prism, which is in contact with analyte material changing its index of refraction (thickness). Changes of the refractive index are monitored by measuring the differential phase shift between p- and s-polarized components of light reflected from the system. We show that due to a high refractive index of Si, such methodology leads to a high sensitivity and dynamic range of measurements. Furthermore, the Si-based platform offers an easy bioimmobilization step and excellent opportunities for the development of multi-channel microsensors taking advantage of the advanced state of development of Si-based microfabrication technologies.

Predicting drug loading in PLA-PEG nanoparticles.

Polymer nanoparticles present advantageous physical and biopharmaceutical properties as drug delivery systems compared to conventional liquid formulations. Active pharmaceutical ingredients (APIs) are often hydrophobic, thus not soluble in conventional liquid delivery. Encapsulating the drugs in polymer nanoparticles can improve their pharmacological and bio-distribution properties, preventing rapid clearance from the bloodstream. Such nanoparticles are commonly made of non-toxic amphiphilic self-assembling block copolymers where the core (poly-[d,l-lactic acid] or PLA) serves as a reservoir for the API and the external part (Poly-(Ethylene-Glycol) or PEG) serves as a stealth corona to avoid capture by macrophage. The present study aims to predict the drug affinity for PLA-PEG nanoparticles and their effective drug loading using in silico tools in order to virtually screen potential drugs for non-covalent encapsulation applications. To that end, different simulation methods such as molecular dynamics and Monte-Carlo have been used to estimate the binding of actives on model polymer surfaces. Initially, the methods and models are validated against a series of pigments molecules for which experimental data exist. The drug affinity for the core of the nanoparticles is estimated using a Monte-Carlo "docking" method. Drug miscibility in the polymer matrix, using the Hildebrand solubility parameter (δ), and the solvation free energy of the drug in the PLA polymer model is then estimated. Finally, existing published ALogP quantitative structure-property relationships (QSPR) are compared to this method. Our results demonstrate that adsorption energies modelled by docking atomistic simulations on PLA surfaces correlate well with experimental drug loadings, whereas simpler approaches based on Hildebrand solubility parameters and Flory-Huggins interaction parameters do not. More complex molecular dynamics techniques which use estimation of the solvation free energies both in PLA and in water led to satisfactory predictive models. In addition, experimental drug loadings and Log P are found to correlate well. This work can be used to improve the understanding of drug-polymer interactions, a key component to designing better delivery systems.