GSURE criterion for unsupervised regularized reconstruction in tomographic diffractive microscopy.

We propose an unsupervised regularized inversion method for reconstruction of the 3D refractive index map of a sample in tomographic diffractive microscopy. It is based on the minimization of the generalized Stein's unbiased risk estimator (GSURE) to automatically estimate optimal values for the hyperparameters of one or several regularization terms (sparsity, edge-preserving smoothness, total variation). We evaluate the performance of our approach on simulated and experimental limited-view data. Our results show that GSURE is an efficient criterion to find suitable regularization weights, which is a critical task, particularly in the context of reducing the amount of required data to allow faster yet efficient acquisitions and reconstructions.

The CONSTANCES Cohort Biobank: An Open Tool for Research in Epidemiology and Prevention of Diseases.

"General-purpose cohorts" in epidemiology and public health are designed to cover a broad scope of determinants and outcomes, in order to answer several research questions, including those not defined at study inception. In this context, the general objective of the CONSTANCES project is to set up a large population-based cohort that will contribute to the development of epidemiological research by hosting ancillary projects on a wide range of scientific domains, and to provide public health information. CONSTANCES was designed as a randomly selected sample of French adults aged 18-69 years at study inception; 202,045 subjects were included over an 8-year period. At inclusion, the selected participants are invited to attend one of the 24 participating Health Prevention Centers (HPCs) for a comprehensive health examination. The follow-up includes a yearly self-administered questionnaire, and a periodic visit to an HPC. Procedures have been developed to use the national healthcare databases to allow identification and validation of diseases over the follow-up. The biological collection (serum, lithium heparinized plasma, EDTA plasma, urine and buffy coat) began gradually in June 2018. At the end of the inclusions, specimens from 83,000 donors will have been collected. Specimens are collected according to a standardized protocol, identical in all recruitment centers. All operations relating to bio-banking have been entrusted by Inserm to the Integrated Biobank of Luxembourg (IBBL). A quality management system has been put in place. Particular attention has been paid to the traceability of all operations. The nature of the biological samples stored has been deliberately limited due to the economic and organizational constraints of the inclusion centers. Some research works may require specific collection conditions, and can be developed on request for a limited number of subjects and in specially trained centers. The biological specimens that are collected will allow for a large spectrum of biomarkers studies and genetic and epigenetic markers through candidate or agnostic approaches. By linking the extensive data on personal, lifestyle, environmental, occupational and social factors with the biomarker data, the CONSTANCES cohort offers the opportunity to study the interplays between these factors using an integrative approach and state-of-the-art methods.

Maternal consumption of quinine-containing sodas may induce G6PD crises in breastfed children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect often presenting with neonatal jaundice and/or hemolytic anemia. G6PD hemolytic events are linked with exposure to a pro-oxidant agent. We here report three cases of initial G6PD crises in breastfed children secondary to maternal consumption of a tonic drink which contains quinine. Quinine was found in breast milk of one of the mothers after she consumed tonic water. CONCLUSION: The amount of quinine that is transmitted through breast milk appears to be sufficient to induce G6PD crises in breastfed children. We hence recommend that consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency. What is Known: • G6PD hemolytic events are linked with exposure to a pro-oxidant agent. • Ingestion of fava beans by a mother who was breastfeeding has been reported to induce a neonatal G6PD crisis. What is New: • Maternal consumption of tonic drink which contains quinine appears to be sufficient to induce G6PD crises in breastfed children. • Maternal consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency.

Prevalence, risk factors and prognosis of hypernatraemia during hospitalisation in internal medicine.

INTRODUCTION: Hypernatraemia in hospitalised patients is less common and less studied than hyponatraemia, although it also seems to be associated with a poor prognosis. The present study evaluates its prevalence, risk factors and prognosis in an internal medicine department. METHODS: Full hospital stays over 28 months in a 36-bed internal medicine department were analysed retrospectively. Patients with at least one plasma sodium ≥ 150 mmol/l were compared first with all other patients and then individually with sex- and age-matched normonatraemic controls. RESULTS: Plasma sodium ≥ 150 mmol÷l was observed during 49÷1945 hospitalisations (2.6%); it was acquired during hospitalisation in 30 cases (61%). Hypernatraemic patients were significantly older with no gender difference. They were comparable with their matched normonatraemic controls regarding the Charlson comorbidity index, although individual comorbidities varied. They were bedridden in 45% vs 15% for controls (p = 0.001). Nearly one-third of hypernatraemic patients had an increased extracellular fluid volume. Hypernatraemia was associated with higher in-hospital mortality (43% vs 2%, p < 0.001) and longer hospitalisation (median 21 vs 10 days, p = 0.004). CONCLUSION: Hypernatraemia is more likely to occur in older and dependent patients and is associated with poor prognosis. Unlike classical teaching, it is often associated with increased extracellular fluid volume, even outside intensive care units.

Reaction of the m-THPC triplet state with the antioxidant Trolox and the anesthetic Propofol: modulation of photosensitization mechanisms relevant to photodynamic therapy?

Antioxidants may affect the outcome of photodynamic therapy (PDT) through the inactivation of reactive oxygen species. Their direct interaction with photosensitizers excited at the triplet state is also worthy of interest. This process is investigated by laser flash photolysis of m-THPC (meso-tetra(3-hydroxyphenyl)chlorin, Foscan) hydroalcoholic solutions added with Trolox (TrOH), a standard antioxidant or Propofol (PfOH, Diprivan(®)), a common anesthetic agent also characterized for its antioxidant properties. Transient UV-visible absorption spectra, kinetics at selected wavelengths and final spectra after extensive laser irradiation show that both compounds react with the m-THPC triplet state, (3)m-THPC, to ultimately restore the photosensitizer in its ground state. For PfOH, this process mainly appears as a single step obeying pseudo-first order kinetics. The bimolecular rate constant for the quenching of (3)m-THPC by PfOH is around 2 × 10(6) M(-1) s(-1), a value increased to some extent by the water content of the solution. A bimolecular reaction between (3)m-THPC and TrOH is observed with a rate constant of similar magnitude and dependence upon water. However, the reaction leads, at least partly, to intermediate species assigned to the TrO˙ radical and the m-THPC anion radical. Within a few ms, these species back react to yield m-THPC in its ground state. A general mechanism involving an intermediate activated complex with some charge transfer character is proposed. Depending on the redox potentials for the oxidation of the antioxidant, this complex evolves predominantly either toward the formation of radicals (TrOH) or back to the photosensitizer ground state (PfOH). Notably, the kinetics data suggest that Propofol may quench (3)m-THPC at concentrations relevant of clinical situation in PDT involving anesthesia.

Modulation of photosensitization processes for an improved targeted photodynamic therapy.

Photodynamic therapy (PDT) is a cancer treatment modality involving the combination of light, a photosensitizer (PS) and molecular oxygen, which results in the production of cytotoxic reactive oxygen species (ROS). Singlet oxygen ((1)O(2)) is one of the most important of these ROS. Because the lifetime and diffusion of (1)O(2) is very limited, a controllable singlet oxygen generation with high selectivity and localization would lead to more efficient and reliable PDT. The lack of selective accumulation of the PS within tumour tissue is a major problem in PDT. Targeted PDT would offer the advantage to enhance photodynamic efficiency by directly targeting diseased cells or tissues. Many attempts have been made to either selectively deliver light to diseased tissues or increase the uptake of the photoactive compounds by the target cells. The review will survey the literature regarding the multi-level control of (1)O(2) production for PDT applications. The mechanisms of ROS formation are described. The different strategies leading to targeted formation of (1)O(2) are developed. Some active PDT agents have been based on energy transfer between PS by control of the aggregation/ disaggregation. The concept of molecular beacon based on quenching-dequenching upon protease cleavage is capable of precise control of (1)O(2) by responding to specific cancer-associated biomarkers.

Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

Reactivity towards singlet oxygen of propofol inside liposomes and neuronal cells.

Singlet oxygen (1O2), a reactive oxygen species, has been found to be implicated in many cellular events and pathological disorders. Herein, we investigated the reactivity of 1O2 towards the anaesthetic agent propofol (PPF) encapsulated within DMPC liposomes. By time resolved luminescence, the rate constant of 1O2 quenching by PPF was evaluated, depending on the location of the sensitizer, with following values: 1.35+/-0.05x10(7) M(-1) s(-1) for deuteroporphyrin (as embedded source) and 0.8+/-0.04x10(7) M(-1) s(-1) for uroporphyrin (as external source), respectively. The nature of the oxidation product, resulting from the reaction of 1O2 with PPF, was determined using absorption and HPLC techniques. Finally, the in vitro protective effect of PPF towards the 1O2-induced neuronal cell toxicity was evaluated in terms of cell viability.

[Developing a questionnaire to evaluate pain in ocular or periocular pathologies: the ODEON questionnaire]. / Création d'un questionnaire destiné à la prise en charge de la douleur dans les pathologies oculaires et/ou péri-oculaires: ODEON - Objectif Douleur En Ophtalmologie et Neuro-ophtalmologie.

INTRODUCTION: Ophthalmologists contend with a wide range of painful acute and chronic diseases. However, there is no tool specific to ocular pain that aids the patient in describing and quantifying pain. PURPOSE: Our objective was to develop a tool that would allow the ophthalmologist to identify the patient's pain quickly and precisely in order to measure its intensity and to determine possible causes. METHODS: An interview guide was elaborated after a literature review. Structured interviews were conducted in hospitals by a clinical research associate with patients suffering from painful acute or chronic pathologies. Different types of quantification and description of pain were proposed to patients. A questionnaire was developed and tested. After the analysis of the tests, the ODEON pilot questionnaire (Objectif Douleur En Ophtalmologie et Neuro-ophtalmologie: target: ophthalmic and neuro-ophthalmic pain) was developed. RESULTS: Twenty patients presenting ten different diagnoses were interviewed. Patients preferred to quantify pain with visual analogic or graduated scales. They appreciated the help of pictograms to describe their pain. Eight other patients presenting six different diagnoses tested the questionnaire. They judged the test version valid and easy to use, except for the section on emotional descriptors. An average of approximately 20 minutes was necessary to complete the questionnaire. After the tests, various questions were combined, reformulated, deleted or added. The ODEON pilot questionnaire contains five sections: 1. general health, 2. eyes and eyesight, 3. pain, 4. pain relief, 5. pictograms and sensorial descriptors. The closed- and open-ended questions included in these dimensions make it possible to measure patient pain and help the practitioner with patient management. CONCLUSION: The ODEON pilot questionnaire was developed under the supervision of a pilot committee involving clinicians and methodologists. Patients have indicated acceptance of this self-administered questionnaire during the cognitive debriefing and it is now being validated.