Parkinsonian gait in elderly people: Significance of the threshold value of two and more falls per year.

OBJECTIVES: Parkinsonism in the elderly presents a major risk factor for recurrent falls (2 and more falls per year), which is associated with increased morbidity. The main objective was to investigate explanatory variables relating to the risk of being recurrent fallers (RF) in persons with parkinsonian gait. METHODS: Seventy-nine among 172 eligible persons were enrolled in this prospective study, the findings of which were analyzed at 12 months. Motor and non-motor features, as well as follow-up interviews to identify falls, loss of ability to walk, fluctuating cognition, traumatic falls, all-cause hospitalizations and deaths were collated and results compared between non RF (zero and one fall per year) and RF. Bayesian model averaging was used to predict the probability of patients being RF from their medical history as well as from cognitive assessment, gait velocity, vision and posture. RESULTS: N=79, 0.58 men, 50% had Parkinson's disease, 14% other neurodegenerative parkinsonian syndrome, 23% vascular parkinsonism and 13% Lewy body disease, 58% were RF. Median age 81.2 years and median MMSE 25/30. A history of falls and of hallucinations, median odds ratio respectively 9.06 (CI 2.34-38.22), 4.21 (CI 1.04-18.67) were associated with the highest odds ratios along with fluctuating cognition and abnormal posture. Two or more falls a year was a relevant threshold to distinguish a population with a high risk of comorbidity. CONCLUSION: The whole history of falls, hallucinations and fluctuating cognition can be considered predictive of recurrent falls in elderly people with parkinsonian gait and provide a tracking tool for patient management.

A synthesis of patterns of environmental mercury inputs, exposure and effects in New York State.

Mercury (Hg) pollution is an environmental problem that adversely affects human and ecosystem health at local, regional, and global scales-including within New York State. More than two-thirds of the Hg currently released to the environment originates, either directly or indirectly, from human activities. Since the early 1800s, global atmospheric Hg concentrations have increased by three- to eight-fold over natural levels. In the U.S., atmospheric emissions and point-source releases to waterways increased following industrialization into the mid-1980s. Since then, water discharges have largely been curtailed. As a result, Hg emissions, atmospheric concentrations, and deposition over the past few decades have declined across the eastern U.S. Despite these decreases, Hg pollution persists. To inform policy efforts and to advance public understanding, the New York State Energy Research and Development Authority (NYSERDA) sponsored a scientific synthesis of information on Hg in New York State. This effort includes 23 papers focused on Hg in atmospheric deposition, water, fish, and wildlife published in Ecotoxicology. New York State experiences Hg contamination largely due to atmospheric deposition. Some landscapes are inherently sensitive to Hg inputs driven by the transport of inorganic Hg to zones of methylation, the conversion of inorganic Hg to methylmercury, and the bioaccumulation and biomagnification along food webs. Mercury concentrations exceed human and ecological risk thresholds in many areas of New York State, particularly the Adirondacks, Catskills, and parts of Long Island. Mercury concentrations in some biota have declined in the Eastern Great Lakes Lowlands and the Northeastern Highlands over the last four decades, concurrent with decreases in water releases and air emissions from regional and U.S. sources. However, widespread changes have not occurred in other ecoregions of New York State. While the timing and magnitude of the response of Hg levels in biota varies, policies expected to further diminish Hg emissions should continue to decrease Hg concentrations in food webs, yielding benefits to the fish, wildlife, and people of New York State. Anticipated improvements in the Hg status of aquatic ecosystems are likely to be greatest for inland surface waters and should be roughly proportional to declines in atmospheric Hg deposition. Efforts that advance recovery from Hg pollution in recent years have yielded significant progress, but Hg remains a pollutant of concern. Indeed, due to this extensive compilation of Hg observations in biota, it appears that the extent and intensity of the contamination on the New York landscape and waterscape is greater than previously recognized. Understanding the extent of Hg contamination and recovery following decreases in atmospheric Hg deposition will require further study, underscoring the need to continue existing monitoring efforts.

Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4.

Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non-haematopoietic tissues. It exists as a membrane-associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily fluids. Despite the proposed use of sDPP4 as a biomarker for multiple diseases, its cellular sources are not well defined. Here, we report that individuals with congenital lymphocyte immunodeficiency had markedly lower serum concentrations of sDPP4, which were restored upon successful treatment and restoration of lymphocyte haematopoiesis. Using irradiated lymphopenic mice and wild-type to Dpp4-/- reciprocal bone marrow chimeric animals, we found that haematopoietic cells were a major source of circulating sDPP4. Furthermore, activation of human and mouse T lymphocytes resulted in increased sDPP4, providing a mechanistic link between immune system activation and sDPP4 concentration. Finally, we observed that acute viral infection induced a transient increase in sDPP4, which correlated with the expansion of antigen-specific CD8+ T cell responses. Our study demonstrates that sDPP4 concentrations are determined by the frequency and activation state of lymphocyte populations. Insights from these studies will support the use of sDPP4 concentration as a biomarker for inflammatory and infectious diseases.

A Third Type of Resistance to Cydia pomonella Granulovirus in Codling Moths Shows a Mixed Z-Linked and Autosomal Inheritance Pattern.

Different isolates of Cydia pomonella granulovirus (CpGV) are used worldwide to control codling moth larvae (Cydia pomonella) in pome fruit production. Two types of dominantly inherited field resistance of C. pomonella to CpGV have been recently identified: Z-chromosomal type I resistance and autosomal type II resistance. In the present study, a CpGV-resistant C. pomonella field population (termed SA-GO) from northeastern Germany was investigated. SA-GO individuals showed cross-resistance to CpGV isolates of genome group A (CpGV-M) and genome group E (CpGV-S), whereas genome group B (CpGV-E2) was still infective. Crossing experiments between individuals of SA-GO and the susceptible C. pomonella strain CpS indicated the presence of a dominant autosomal inheritance factor. By single-pair inbreeding of SA-GO individuals for two generations, the genetically more homogenous strain CpRGO was generated. Resistance testing of CpRGO neonates with different CpGV isolates revealed that isolate CpGV-E2 and isolates CpGV-I07 and -I12 were resistance breaking. When progeny of hybrid crosses and backcrosses between individuals of resistant strain CpRGO and susceptible strain CpS were infected with CpGV-M and CpGV-S, resistance to CpGV-S appeared to be autosomal and dominant for larval survivorship but recessive when success of pupation of the hybrids was considered. Inheritance of resistance to CpGV-M, however, is proposed to be both autosomal and Z linked, since Z linkage of resistance was needed for pupation. Hence, we propose a further type III resistance to CpGV in C. pomonella, which differs from type I and type II resistance in its mode of inheritance and response to CpGV isolates from different genome groups.IMPORTANCE The baculovirus Cydia pomonella granulovirus (CpGV) is registered and applied as a biocontrol agent in nearly all pome fruit-growing countries worldwide to control codling moth caterpillars in an environmentally friendly manner. It is therefore the most widely used commercial baculovirus biocontrol agent. Since 2005, field resistance of codling moth to CpGV products has been observed in more than 40 field plantations in Europe, threatening organic and integrated apple production. Knowledge of the inheritance and mechanism(s) of resistance is indispensable for the understanding of host response to baculovirus infection on the population level and the coevolutionary arms race between virus and host, as well as for the development of appropriate resistance management strategies. Here, we report a codling moth field population with a new type of resistance, which appears to follow a highly complex inheritance in regard to different CpGV isolates.

Association between delirium and cognitive change after cardiac surgery.

BACKGROUND: Previous studies provide inconsistent data on whether postoperative delirium (POD) is a risk factor for postoperative cognitive decline (POCD). We thus investigated the relationship between POD and cognitive change after cardiac surgery and assessed the relationship between preoperative cognitive domain scores and POD. METHODS: Postoperative delirium was assessed with the Confusion Assessment Method (CAM) adapted for the intensive care unit and the conventional CAM accompanied by chart review. Cognitive function was assessed with a neuropsychological test battery before elective cardiac surgery and 1 month and 1 yr afterwards. Cognitive change was calculated using the Reliable Change Index (RCI). Multiple linear regression was used to adjust for confounding. RESULTS: Of the 184 patients who completed baseline assessment, 23 (12.5%) developed POD. At 1 month, the decline in cognitive performance was worse in patients with POD [median composite RCI -1.00, interquartile range (IQR) -1.67 to 0.28] than in patients without POD (RCI -0.04, IQR -0.70 to 0.63, P =0.02). At 1 yr, both groups showed cognitive improvement on average compared with baseline (POD patients median composite RCI 0.25, IQR -0.42 to 1.31, vs non-POD patients RCI 0.92, IQR 0.18-1.53; P =0.08). Correction for differences in age and level of education did not change the results. Patients with POD performed less well than patients without POD on the preoperative Trailmaking test part A ( P =0.03). CONCLUSIONS: Postoperative delirium is independently associated with cognitive decline 1 month after surgery, but cognitive performance generally recovers in 1 yr. Patients with a predisposition to POD can be identified before surgery by worse performance in an attention task. CLINICAL TRIAL REGISTRATION: NCT00293592.

[Assessment method of cognitive load and stress inducer factors of surgeons and anesthetists in the operating room]. / Méthodes d'évaluation de la charge cognitive et des facteurs inducteurs de stress des chirurgiens et anesthésistes au bloc opératoire.

INTRODUCTION: For many years, surgeons and anesthetists have recognized that stress can be present in their daily professional practice. The goal of this study was to identify tools for assessing stress and cognitive load in the operating room. MATERIAL AND METHODS: We conducted a literature review in the PubMed database of scientific articles published on the subject without date limit using the keywords anesthesia, surgery, surgeon, cognitive workload, definition, pathophysiology, physiological measurement, objective, subjective, stress. RESULTS: Nineteen articles were selected, focusing on cardiac surgery, gastrointestinal surgery, vascular surgery and urology. No publications concerning ophthalmology were found through the literature search. The means of measurement found were either subjective, such as questionnaires, or objective, such as the study of heart rate variability (HRV), reaction time, eye movements, electrical conductivity of the skin, biological markers and electroencephalogram. Of all these measurement tools, the NASA-TLX questionnaire, used in four articles, and the HRV study, used in eight articles, appear to be the most widely used and are strongly correlated with stress. CONCLUSION: The articles reviewed use only some of the available tools for assessment of stress and cognitive load. The main objective is to improve the quality of care and the quality of life of caregivers. It would be interesting to develop other methods to identify and better characterize the risk factors that increase stress and cognitive load.

Long-term treatment with empagliflozin, a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats.

Empagliflozin is a potent, selective sodium glucose co-transporter-2 inhibitor that is in development for the treatment of type 2 diabetes. This series of studies was conducted to assess the in vivo pharmacological effects of single or multiple doses of empagliflozin in Zucker diabetic fatty rats. Single doses of empagliflozin resulted in dose-dependent increases in urinary glucose excretion and reductions in blood glucose levels. After multiple doses (5 weeks), fasting blood glucose levels were reduced by 26 and 39% with 1 and 3 mg/kg empagliflozin, respectively, relative to vehicle. After 5 weeks, HbA1c levels were reduced (from a baseline of 7.9%) by 0.3 and 1.1% with 1 and 3 mg/kg empagliflozin, respectively, versus an increase of 1.1% with vehicle. Hyperinsulinaemic-euglycaemic clamp indicated improved insulin sensitivity with empagliflozin after multiple doses versus vehicle. These findings support the development of empagliflozin for the treatment of type 2 diabetes.

Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.

AIMS: Empagliflozin is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT-2 inhibitors. METHODS: [(14)C]-alpha-methyl glucopyranoside (AMG) uptake experiments were performed with stable cell lines over-expressing human (h) SGLT-1, 2 and 4. Two new cell lines over-expressing hSGLT-5 and hSGLT-6 were established and [(14)C]-mannose and [(14)C]-myo-inositol uptake assays developed. Binding kinetics were analysed using a radioligand binding assay with [(3)H]-labelled empagliflozin and HEK293-hSGLT-2 cell membranes. Acute in vivo assessment of pharmacokinetics was performed with normoglycaemic beagle dogs and Zucker diabetic fatty (ZDF) rats. RESULTS: Empagliflozin has an IC(50) of 3.1 nM for hSGLT-2. Its binding to SGLT-2 is competitive with glucose (half-life approximately 1 h). Compared with other SGLT-2 inhibitors, empagliflozin has a high degree of selectivity over SGLT-1, 4, 5 and 6. Species differences in SGLT-1 selectivity were identified. Empagliflozin pharmacokinetics in ZDF rats were characterised by moderate total plasma clearance (CL) and bioavailability (BA), while in beagle dogs CL was low and BA was high. CONCLUSIONS: Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1. Empagliflozin represents an innovative therapeutic approach to treat diabetes.

Heat stability of micellar casein concentrates as affected by temperature and pH.

The increased interest in using micellar casein concentrates (MCC) obtained by microfiltration in the manufacture of shelf-stable high-protein beverages creates a need to understand the effect of sterilization treatments on the stability of this ingredient. The goals of this work were to (1) elucidate the effects of pH and heat treatment temperatures in the sterilization range on the stability of MCC, and (2) use the generated knowledge to develop solutions for stabilizing the MCC during sterilization treatments. Micellar casein concentrate powders were reconstituted, and the resulting casein dispersions were adjusted to pH values of 6.5 to 7.3. Subsequently, the MCC samples were heated in an oil bath to 110 to 150°C. The treated samples were evaluated for particle size, soluble minerals, and casein dissociation. At pH <6.7, all heat-treated samples were visibly aggregated or coagulated. At pH 6.9, higher temperatures led to increased particle size, whereas at pH >6.9, few or no changes were observed after heat treatment. Casein dissociation increased with increasing pH for all caseins, at all temperatures, with dissociation of κ-casein and ß-casein being the most pronounced. At higher pH, the levels of dissociated α(s)-casein decreased after heat treatment, suggesting aggregation of α(s)-casein in the presence of Ca and protection lost by κ-casein. It was concluded that increased stability of MCC requires increasing the pH or lowering the processing temperature. After applying these modifications, MCC was submitted to both retorting and UHT sterilization, at equivalent lethality. A significant reduction in particle size was obtained and no coagulation or aggregation occurred after retorting or UHT under the modified conditions as compared with the controls. The knowledge generated in this study will allow the effective stabilization of MCC in practical applications, such as the production of high-protein, shelf-stable beverages.

Steady shear rheological properties of micellar casein concentrates obtained by membrane filtration as a function of shear rate, concentration, and temperature.

The use of casein preparations obtained by membrane separation is receiving increasing interest from the dairy and food industry. The objective of this work was to generate information about the steady shear rheological properties of micellar casein concentrates (MCC) and the effect of composition, temperature, and shear rate on these properties. Micellar casein concentrate preparations with 2 levels of serum proteins (SP; 65 and 95% SP reduced, respectively), were obtained from skim milk by microfiltration followed by spray drying. Micellar casein concentrate preparations with casein concentrations ranging from 2.5 to 12.5% were obtained by dispersing the MCC powders in ultrapure water. Steady shear rheological analyses at temperatures ranging from 0 to 80°C were performed using a strain-controlled rheometer. Viscosity versus shear rate curves were used to evaluate the effect of shear on viscosity, and the apparent viscosity at a shear rate of 100 s(-1) was used to make direct comparisons between various concentration and temperature conditions. The 65% SP-reduced MCC had lower viscosity than the 95% SP-reduced MCC at the same casein concentration and temperature. Protein preparations at casein concentrations above 7.5% displayed shear-thinning behavior, which was more pronounced as concentration increased. The viscosity of MCC increased exponentially with casein concentration and decreased with temperature. The dependency of viscosity on temperature followed an Arrhenius relationship. A modified Arrhenius model able to accurately predict rheological properties under desired shear, temperature, and concentration conditions was developed and validated. This study provides critical rheological data necessary for developing practical applications of micellar casein preparations.

The effect of commercial sterilization regimens on micellar casein concentrates.

This work focused on evaluating the effects of UHT sterilization and in-container retorting on the stability and physical properties of micellar casein concentrates (MCC). The study was performed on MCC obtained by membrane separation, with casein concentrations between 5 and 10%. The UHT and retorting regimens were designed to achieve the same microbial inactivation effect. Ultra-high temperature treatment was performed in a pilot-scale MicroThermics heating system (MicroThermics Inc., Raleigh, NC), and retorting in an FMC multipurpose laboratory retort (Steritort; FMC Corp., San Jose, CA). The heat-treated and the non-heat-treated MCC controls were evaluated for pH, mineral profile, ζ-potential, particle size, and rheological properties for up to 24h after heat treatment. The treatments were performed in triplicate, and differences among samples were evaluated using statistical analyses. Retorting resulted in slight aggregation in the MCC, whereas UHT caused the formation of visible aggregates and coagulation. The UHT-treated MCC had higher viscosity than retorted MCC, and displayed predominantly solid-like rheological behavior, indicative of structure formation. These effects were, at least in part, attributed to a change in mineral equilibrium, which affected the stability of the casein micelles, but additional mechanisms such as κ-casein dissociation may also play a significant role in these heat-induced changes. Drying of MCC accentuated the observed instabilities, as dried and reconstituted micellar casein concentrates (R-MCC) were more unstable to UHT sterilization than the MCC that had not undergone drying. The results of this study provide valuable information about the sterilization behavior and physical properties of MCC, which can be useful to processors in the development and manufacture of shelf-stable casein-based products and beverages.

Inactivation of Escherichia coli in milk and concentrated milk using pulsed-light treatment.

Pulsed light (PL) treatment has been viewed as an alternative to thermal treatments for the inactivation of pathogenic and spoilage microorganisms in recent years. The objectives of this study were to quantify the effectiveness of PL on inactivating Escherichia coli in cow milk and to evaluate the effect of total solids and fat content on inactivation. Samples of reconstituted milk with variable total solids levels (9.8, 25, and 45%) and commercial cow milk with different fat contents (skim milk, 2% fat, and whole milk) were inoculated with nonpathogenic E. coli ATCC 25922 at a concentration of 10(7)cfu/mL. One milliliter of the inoculated sample was placed in a thin layer in a glass chamber and exposed to PL doses of up to 14.9 J/cm(2), both in static mode and turbulent mode. Survivors were quantified using standard plate counting. All experiments were performed in triplicate. Pulsed light treatment of the concentrated milks of 25 and 45% solids content resulted in reductions of less than 1 log, even in turbulent mode, whereas for the milk with 9.8% solids content, reduction levels of 2.5 log cfu were obtained after treatment with 8.4 J/cm(2) in turbulent mode. In the skim milk, a 3.4 log cfu reduction at 14.9 J/cm(2) was obtained and a plateau of the inactivation curve typical of PL treatment was not achieved. Under the same conditions, both 2% and whole milk attained inactivation levels greater than 2.5 log cfu. These data indicate that PL is effective for the inactivation of E. coli in milk, but has limited effectiveness for microbial inactivation in concentrated milk, due to the absorption of light by the milk solids and shielding of the bacteria in the concentrated substrates. Milk fat also diminishes the effectiveness of PL to some extent, due to light-scattering effects.

[Ocular surface and outdoor air pollution: A systematic review]. / Surface oculaire et pollution environnementale extérieure : revue systématisée de la littérature.

INTRODUCTION: Air pollution has steadily increased for several decades, with widely studied effects on human health, including increased mortality, incidence of stroke, respiratory and allergic disease. However, the effects of pollution on the ocular surface, in direct contact with the outside world, have been less precisely studied. MATERIALS AND METHODS: We conducted a literature review of articles on the subject published from 1966 to October 2020. Among the 661 articles identified, 33 were retained. Ocular surface disease associated with pollution included non-specific conjunctivitis, dry eye disease, blepharitis, and allergic conjunctivitis. The studied pollutants were particulate matter less than 2.5µm and 10µm (PM2.5, PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and sulfur dioxide (SO2). Certain air quality parameters such as temperature and relative humidity were also studied. RESULTS: Among the markers of air pollution possibly associated with ophthalmic disease, NO2 and SO2 appear to be the most frequent and highly correlated. High temperatures and low humidity levels also appear to be aggravating factors for the ocular surface. However, due to the heterogeneity of the studies, the results must be interpreted with caution. Indeed, the methodology and the results of the various studies are sometimes contradictory. The inclusion of patients, the analysis of environmental data, and the correlation between these two elements indeed raise numerous methodological questions. CONCLUSION: Air pollution control would appear essential, as well as the development of new studies based on reliable methods of studying the environmental and its clinical effects.

[Digital eye strain. Functional symptoms and binocular balance analysis in intensive digital users]. / Stress oculaire induit par les écrans. Analyses des symptômes fonctionnels et de l'équilibre binoculaire chez des utilisateurs intensifs.

INTRODUCTION: In almost 50 % of cases, acute or chronic screen exposure is accompanied by symptoms of dry eye or binocular imbalance, known as digital eye strain. This phenomenon is described relatively little in the literature. The goal of this study is to determinate the effects of screen exposure on subjective comfort and binocular balance. PATIENTS AND METHODS: This is a cross-sectional, prospective, monocentric pilot study conducted from August to October 2019. The first part of the study focused on disturbances induced by short-term screen exposure (comparison between morning and evening examinations) between a control group (less than 5hours a day) and an exposed group (more than 5hours a day). The second part investigates the consequences of chronic exposure (screen exposure greater than 5hours a day, 5 days a week for one year) excluding pre-presbyopic and presbyopic patients (over 35 years of age). The study parameters consisted of an ocular discomfort questionnaire and binocular function tests (refraction, phoria, near point of accommodation and convergence, fusional vergence (FV), and binocular amplitude facility (BAF)). RESULTS: Short exposure : 52 participants were included. No significant difference was found between the control group (n=24, mean exposure=2.6 hr) and the exposed group (n=28, mean exposure=6.1 hr) for any of the objective parameters. The ocular discomfort score was highest in the exposed group for the following parameters: near (p=0.04) and intermediate (p=0.02) blurred vision and light sensitivity (p=0.04). Chronic exposure: 35 participants were included. The exposed group (n=12, mean exposure=6.7 hr) showed a decrease in FV (p=0.045) and BAF (p=0.038) compared to the control group (n=23, mean exposure=2.1 hr). DISCUSSION: Binocular balance is disturbed by intensive and chronic use of screens. Special attention must therefore be paid to these patients.

Non-opioid analgesics and post-operative pain following transoral robotic surgery for oropharyngeal cancer.

OBJECTIVE: To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma. METHODS: Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis. RESULTS: A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1-T2 tumours, and 82.9 per cent had stage N0-N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin. CONCLUSION: Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.

[Management of ocular toxoplasmosis in France: Results of a modified Delphi study]. / Prise en charge de la toxoplasmose oculaire en France : résultats d'une étude Delphi modifiée.

OBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.

[Digital eye strain. Symptoms, prevalence, pathophysiology, and management]. / Perturbations oculaires secondaires à l'utilisation de supports numériques. Symptômes, prévalence, physiopathologie et prise en charge.

The digital revolution, which has been underway since the 1980's, is disrupting our daily routines with an exponential increase in the use of screens, which has not been without consequence to our visual system. Digital eye strain (DES), or computer vision syndrome (CVS), includes all the visual symptoms secondary to the use of digital devices. DES is present in at least 50% of regular users of digital media and is defined by blurred vision, difficulty focusing, ocular irritation or burning, dry eye, visual fatigue, headaches and increased sensitivity to light. Exposure time, age, female gender, and work environment are the main factors increasing its prevalence. Its pathophysiology, still poorly understood, is felt to be multifactorial and includes disturbances in the accommodative-convergence balance and changes in the ocular surface. Regarding accommodation and convergence, the studies are mostly old and their results heterogeneous. Conversely, many studies have shown an increase in the prevalence of dry eye in screen users. Although the retinal toxicity of blue light has been proven in in vitro models, the low level of evidence in the available studies does not allow it to be clearly correlated with the symptoms of DES. The objective of this review is to condense the knowledge available in the literature on the symptoms, prevalence, pathophysiology and management of DES.

Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters.

ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.

Does heart surgery change the capacity of α1-antitrypsin to inhibit the ATP-induced release of monocytic interleukin-1ß? A preliminary study.

Heart surgery involving cardiopulmonary bypass induces systemic inflammation that is, at least in part, caused by extracellular ATP originating from damaged cells and by proteases secreted by activated neutrophils. The anti-protease α1-antitrypsin (AAT) forms complexes with several proteases including neutrophil elastase, resulting in a mutual loss of activity. We demonstrated recently that AAT inhibits the ATP-induced release of the pro-inflammatory cytokine interleukin-1ß by human monocytes by a mechanism involving activation of metabotropic functions at nicotinic acetylcholine receptors. Interleukin-1ß importantly contributes to the pathogenesis of sterile inflammatory response syndrome. Thus, AAT might function as an endogenous safeguard against life-threatening systemic inflammation. In this preliminary study, we test the hypothesis that during cardiopulmonary bypass, AAT is inactivated as an anti- protease and as an inhibitor of ATP-induced interleukin-1ß release. AAT was affinity-purified from the blood plasma of patients before, during and after surgery. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with ATP in the presence or absence of patient AAT to test for its inhibitory effect on interleukin-1ß release. Anti-protease activity was investigated via complex formation with neutrophil elastase. The capacity of patient AAT to inhibit the ATP-induced release of interleukin-1ß might be slightly reduced in response to heart surgery and complex formation of patient AAT with neutrophil elastase was unimpaired. We conclude that surgery involving cardiopulmonary bypass does not markedly reduce the anti-inflammatory and the anti-protease activity of AAT. The question if AAT augmentation therapy during heart surgery is suited to attenuate postoperative inflammation warrants further studies in vivo.

[Vision screening in children: Review of the literature]. / Dépistage visuel de l'enfant : revue de la littérature.

In children, refractive errors and amblyopia are the two most common causes of avoidable visual impairment. Screening for these is essential, especially since there is a so-called "sensitive" period during which the maturation of the visual pathways is not complete. The child's visual prognosis will therefore depend on his or her age, the duration of the visual deprivation and the timing of management. Visual screening is part of a public health approach, but there are significant regional disparities regarding its organization and the means used. We conducted a review of the literature in order to establish an inventory of available resources and improve practices.