Mesoporous organosilicas with highly-content tyrosine framework as extractive phases for non-steroidal anti-inflammatory drugs in aquatic media.

BACKGROUND: Attentions regarding ordered mesoporous silica materials (OMSs), with large specific surface areas and narrow pore size distribution, which are prepared via self-assembly techniques, have been raised in sorption, separation, and sample preparation. However, in order to extend and improve their applications, a functionalization step is required. Organic units can be anchored on the inner or outer surface as well as in the silica wall framework by co-condensation-, grafting-, and periodic mesoporous organosilica (PMO) preparation approaches. Apparently, by synthesizing PMO with extensive and flexible organic bridging groups within the mesoporous wall, an efficient extractive phase can be achieved. RESULTS: We employed tyrosine amino acid to synthesize a PMO-based extractive phase. The FT-IR, 1H NMR, HR-ESI-MS, Low angle-XRD, TEM, FESEM, BET, and EDX-MAP analyses confirmed the successful synthesis of PMO within the salt-assisted templating method. A comprehensive study on sorption behavior of PMO was performed and its efficiency was evaluated against the grafting and co-condensation methods. Then, it was implemented to the pipette tip-micro solid phase extraction (PT-µ-SPE) of widely used non-steroidal anti-inflammatory drugs (NSAIDs) in water/wastewaters. Limits of detection and quantification were obtained in the range of 0.1-1.5 and 0.3-5 µg L-1, respectively. The calibration plots are linear in the 1-1000, 3-1000, 10-750, and 3-750 µg L-1, respectively. The intra-and inter-day precision at 50 and 200 µg L-1 levels are 2.9-7.1 % and 3.5-8%, while recoveries are between 84 and 111 %. SIGNIFICANCE: High-capacity tyrosine functionalized PMO with 2D hexagonal symmetry silica mesoporous structures found to be highly efficient extractive media. Despite the bulkiness and flexibility of the bridging group within the mesoporous wall, the synthesis condition was optimized in order to load more organic content in the PMO structure. The PMO performance was superior over organically modified ordered mesoporous silica materials prepared by the grafting and co-condensation methods.

Breathing in the future: prenatal exposure to air pollution and infants' health outcomes in the USA.

OBJECTIVES: This study aimed to investigate the impact of air pollution on birth outcomes in the USA over several decades. STUDY DESIGN: Approximately 70 million birth records were assessed for the years 1980-2020. This study focussed on seven measures of birth outcomes, including birth weight, low birth weight, very low birth weight, full-term birth weight, foetal growth, gestational age and very premature birth. METHODS: An instrumental variable identification strategy was used that exploited within county-month and within month-year of birth variations in exposure to precipitation-induced changes in air pollution. RESULTS: Air pollution was found to have negative and large effects on a wide range of birth outcomes. The study findings suggest that a one-standard-deviation increase in ozone was associated with a 6.4% and 12.8% increase (from the mean) in the proportion of low birth weight and very preterm birth infants, respectively. Further analyses suggest that these effects were heterogeneous across trimesters of pregnancy and reveal larger impacts during the second and third trimesters. CONCLUSIONS: The results suggest that the ordinary least square estimates of previous studies considerably underestimate the true effects of pollution on birth outcomes. Policies that aim to improve the health capital of future generations should allocate more resources and initiatives to improving environmental air quality.

[Antidepressive agents and hypertension: A case/no-case study in French pharmacovigilance database]. / Antidépresseurs et hypertension artérielle : étude cas /non-cas dans la base nationale de pharmacovigilance.

INTRODUCTION: Drug-induced hypertension was described with several pharmacological classes. The association between hypertension and antidepressant drugs (AD) is controversial. The objective of this study was to evaluate the link between hypertension and ADs. MATERIALS AND METHODS: A retrospective disproportionality analysis from observations consecutively reported to the French pharmacovigilance database between 1985 and 2020 was performed. The relationship between the suspected ADs and the occurrence of hypertension was assessed by calculating the reporting odds ratio (ROR) in a case/non-case design. A negative (paracetamol) and a positive (celecoxib) control were used to validated this disproportionality method. RESULTS: We compared 6725 cases (including 464 AD-related cases) to 789,483 non-cases (including 56,440 AD-related cases). The reporting of hypertension was significantly associated with serotonin/norepinephrine reuptake inhibitors (SNRI) (ROR 1.43, 95 % CI 1.26-1.64) and monoamine oxidase inhibitors (MAOI) (ROR 6.41, 95 % CI 4.25-9.67) but not with other ADs classes. Concerning ADs analyzed independently of their AD class, a significant signal was observed with many SNRIs (duloxetin, milnacipran and venlafaxin) and with all MAOIs (moclobemide, iproniazide) (ROR between 2.04 and 17.93) but not with others ADs. The ROR value of positive (celecoxib) and negative (paracetamol) controls were ROR=1.53; IC95 %=1.04-2.26 and ROR=0.72; IC95 %=0.65-0.80, respectively. CONCLUSION: We found a significant association between development or worsening of hypertension and SNRIs and MAOIs but not with others ADs, in this study performed in real conditions of life. It is therefore advisable to remain cautious when prescribing ADs and to check systematically for hypertension.

Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

Cardiovascular risk profile of patients with peripheral arterial occlusive disease during nilotinib therapy.

BACKGROUND: Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. OBJECTIVE: We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). PATIENTS/METHODS: We selected all cases of "vascular disorders," as the System Organ Class in MedDRA®, in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. RESULTS: We identified 25 cases of POAD. Most of the patients were older than 60 years (84 %) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72 %). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24 months and was significantly longer in patients aged less than 60 years compared with those aged over 60 years (33.8 ± 24.6 months vs. 22.6 ± 17.5 months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. CONCLUSIONS: The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60 years of age; in patients younger than 60 years of age, long-term surveillance has to be maintained.

[Drug-induced pancreatitis. A review of French spontaneous reports]. / Pancréatites d'origine médicamenteuse. Revue des notifications spontanées en France.

PURPOSE: Identify the main pharmacological classes inducing pancreatitis using spontaneous reports recorded in the French pharmacovigilance database (FPVD). METHODS: Cases of pancreatitis recorded in FPVD between January 1st 1985 and December 31st 2013 were selected using the 2001 consensus conference criteria of the French High Health Authority. RESULTS: During this period, 2975 observations were selected with 1151 fulfilling criteria of drug-induced pancreatitis (i.e. 0.22% of total notifications in the FPVD). According to ATC classification, the pharmacological classes most frequently found were antiretroviral, analgesic, lipid-lowering, immunosuppressive and insulin secreting drugs. For some drugs (metformin, omeprazole, etc.) pancreatitis was "unlabelled" in the summary of product characteristics. CONCLUSION: This review allows to identify the main drug classes currently involved in spontaneous reporting of pancreatitis in France.

Ischaemic stroke after exposure to aflibercept: interaction with vitamin K antagonist and/or direct pharmacodynamic effect?

WHAT IS KNOWN AND OBJECTIVE: Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD). CASE SUMMARY: We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive. WHAT IS NEW AND CONCLUSION: A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.

[Hospital readmission induced by adverse drug reaction: a pilot study in a post-emergency unit of a French university hospital]. / Réhospitalisations d'origine médicamenteuse : étude pilote dans un service de post-urgences médicales d'un hôpital universitaire français.

PURPOSE: Adverse Drug Reactions (ADRs) leading to hospital admission was estimated to 3.6 to 21.7%. Despite its importance in terms of patients care, readmission to hospital due to ADRs remains poorly documented. The aim of our study was to investigate the rate and main characteristics of readmission for ADRs. METHODS: We undertook a retrospective study during two years (2011-2012) in the post-emergency unit of Toulouse university hospital (south western, France). We selected all unplanned hospitalization for acute disease and included all cases of patients admitted twice fold or more for ADRs. Characteristics of drug-induced ADRs were assessed according to appropriate use or not. RESULTS: Out of the 197 readmitted patients, 71 was related to ADRs (3.6%) corresponding to 17.8‰ patients-year. Mean age was 82.3 years and 67% were women. The most frequent ADRs found were vascular (n=41, 18.4%), gastro-intestinal (n=28, 12.6%), cardiac (n=28, 12.6%), neurologic (n=26, 11.7%), metabolic (n=26, 10.3%) and psychiatric (n=24, 9.9%). The drugs mainly involved were psychoactive, cardiovascular, digestive or antithrombotic agents. The context of occurrence of ADRs was related to inappropriate drug prescription in 56% of cases. A total of 24 patients were admitted twice for the same ADR and 2 others three times. For 22 patients (30.9%), the same drugs were involved. CONCLUSION: Our data show hospital readmission was due to ADRs in 3.6% of cases. In 1.1% of cases, the same couple "drug-ADR" was involved. Furthermore, in 56% of cases, repeated admissions are related to an inappropriate drug prescription.

From antiretroviral originator to generic drugs: bioequivalence and pharmacovigilance.

UNLABELLED: Antiretroviral drugs have been available in generic form in developing countries, which has expanded access to treatment; they have also become available in developed countries more recently. OBJECTIVES: The validation of generic drugs (GD) compared to originator drugs (OD) is mandatory to ensure that using generics will lead to a decreased cost of treatment. RESULTS: The results were obtained by analyzing published data as well as European Medicines Agency recommendations. METHOD: The GD should have the same qualitative and quantitative active principle formula, the same pharmaceutical forms, and the same criteria in terms of quality, effectiveness, and safety. This equivalence is based on bioequivalence rules: comparison of the concentration/time curves (AUC); Cmax and Tmax (90%), for which the confidence intervals in the range of 80-125% should be included. Naturally, that does not mean that the concentrations can vary from 80 to 125%: this would indicate unacceptable deviations. Conforming to these criteria allows substituting an OD by a GD. Adverse effects should not be different from those observed for the OD. Adverse effects observed when the GD is used must be notified, as is the case for the OD. Accountability is established according to 4 essential pieces of information: a prescriber, a patient, a drug, and an adverse effect. It is sometimes difficult to identify the provider of the GD that has been delivered. CONCLUSION: The level of safety concerning effectiveness and tolerance required is identical for OD and GD, in Europe. Analyzing confirmed adverse effects and therapeutic failures is the only way to identify differences that could question a GD's effectiveness.

Interaction effects of cell diffusion, cell density and public goods properties on the evolution of cooperation in digital microbes.

Microbial cooperation typically consists in the sharing of secreted metabolites (referred to as public goods) within the community. Although public goods generally promote population growth, they are also vulnerable to exploitation by cheating mutants, which no longer contribute, but still benefit from the public goods produced by others. Although previous studies have identified a number of key factors that prevent the spreading of cheaters, little is known about how these factors interact and jointly shape the evolution of microbial cooperation. Here, we address this issue by investigating the interaction effects of cell diffusion, cell density, public good diffusion and durability (factors known to individually influence costs and benefits of public goods production) on selection for cooperation. To be able to quantify these effects across a wide parameter space, we developed an individual-based simulation platform, consisting of digital cooperator and cheater bacteria inhabiting a finite two-dimensional continuous toroidal surface. Our simulations, which closely mimic microbial microcolony growth, revealed that: (i) either reduced cell diffusion (which keeps cooperators together) or reduced public good diffusion (which keeps the public goods closer to the producer) is not only essential but also sufficient for cooperation to be promoted; (ii) the sign of selection for or against cooperation can change as a function of cell density and in interaction with diffusion parameters; and (iii) increased public goods durability has opposing effects on the evolution of cooperation depending on the level of cell and public good diffusion. Our work highlights that interactions between key parameters of public goods cooperation give rise to complex fitness landscapes, a finding that calls for multifactorial approaches when studying microbial cooperation in natural systems.

Adverse drug reactions in an emergency medical dispatching centre.

PURPOSE: The purpose of this study is to assess the incidence of adverse drug reactions (ADR) leading to call an emergency medical dispatching centre. METHODS: A prospective, observational, monocentric clinical study performed over a 2-year period (2011-2012) in a French prehospital emergency dispatching centre, the Service d'Aide Médicale Urgente (SAMU) covering 1,156,000 inhabitants. All adult patients (age≥18) who called for any cause were included. We created an electronic trigger 'iatrogenic event' implemented by the dispatching physician for each suspected case of ADR, then we completed the analyses of all the cases with a chief complain represented in more than 1% of the triggered cases. The primary outcome variable was the occurrence of any possible ADR. We then used the French method of causal relationship assessment. RESULTS: The SAMU dispatched 339,915 calls during the study. In total, 1,467 ADRs were identified, representing 0.95% (CI 95% 0.90-1.00%) of cases. ADRs were as serious (SADR) in 51.06% (CI 95% 48.45-53.67%) of cases. The major ADR observed was haemorrhage, (42.81% (CI 95% 40.62-45.00%), n=628) followed by allergy, hypoglycaemia, vomiting, dizziness and drowsiness. The class of drugs most frequently involved was antithrombotic (43.69% (CI 95% 41.45-45.93%), n=641), followed by insulin (17.98% (CI 95%:17.06-18.90%), n=264). CONCLUSIONS: Emergency calls concerning ADRs were estimated as 9/1,000, and one out of two is serious.

Analysis of patients' narratives posted on social media websites on benfluorex's (Mediator® ) withdrawal in France.

WHAT IS KNOWN AND OBJECTIVE: Websites and discussion lists on health issues are among the most popular resources on the Web. Use experience reported on social media websites may provide useful information on drugs and their adverse reactions (ADRs). Clear communication on the benefit/harm balance of drugs is important to inform proper use of drugs. Some data have shown that communication (advisories or warnings) is difficult. This study aimed to explore the Internet as a source of data on patients' perception of risk associated with benfluorex and the impact of wider media coverage. METHODS: Three French websites were selected: Doctissimo, Atoute.org considered the best-known and visited website in France for health questions and Vivelesrondes (Long live the Tubbies) for overweight people. Three periods were chosen: (1) before November 2009 (i.e. before benfluorex withdrawal), (2) between November 2009 and November 2010 (when the risk of valvulopathy with benfluorex appeared in social media) and (3) after November 2010. RESULTS AND DISCUSSION: Two hundred twenty initial postings were analysed. These lead to 660 secondary postings which were analysed separately. In period 1, 114 initial postings were analysed, mostly concerning efficacy of the drug (72%). In period 2, 42 initial postings were analysed involving mainly ADRs or warnings (73%). In period 3, 64 initial postings were analysed; most frequent expressing anger directed at the healthcare system (58%) and anxiety about cardiovascular ADRs (30%). Online consumer postings showed that there were drastic changes in consumers' perceptions following media coverage. WHAT IS NEW AND CONCLUSION: This study suggests that analysis of website data can inform on drug ADRs. Social media are important for communicating information on drug ADRs and for assessing consumer behaviour and their risk perception.

The structure of clinical consultation: a case of non-native speakers of English as participants.

BACKGROUND: In many parts of the world, patients may find it difficult to visit doctors who share the same language and culture due to the intermingling of people and international recruitment of doctors among many other reasons. In these multilingual multicultural settings (MMSs), doctor-patient interactions face new communication challenges. This study aims to identify the structure of clinical consultation and its phases in an MMS where both doctors and patients are non-native speakers (NNSs) of English. METHOD: This study takes on a discourse analytic approach to examine the structure of clinical consultation as an activity type. 25 clinical consultation sessions between non-native speakers of English in a public healthcare centre in Malaysia were audio-recorded. FINDINGS & DISCUSSION: The results show that there are some deviations from the mainstream structure of clinical consultations although, in general, the pattern is compatible with previous studies. Deviations are particularly marked in the opening and closing phases of consultation. CONCLUSION: In almost all interactions, there is a straightforward manner of beginning medical consultations. The absence of greetings may have naturally reduced the length of talk. Hence, by directly entering medical talks, the doctors voice their concern on the curing aspects of the consultation rather than its caring facets. The preference of curing priority to caring is more goal-oriented and in alignment with the consultation as an activity type.

Environmental, developmental, and genetic factors controlling root system architecture.

A better understanding of the development and architecture of roots is essential to develop strategies to increase crop yield and optimize agricultural land use. Roots control nutrient and water uptake, provide anchoring and mechanical support and can serve as important storage organs. Root growth and development is under tight genetic control and modulated by developmental cues including plant hormones and the environment. This review focuses on root architecture and its diversity and the role of environment, nutrient, and water as well as plant hormones and their interactions in shaping root architecture.

Effects of cyclic static stretch on fatigue recovery of triceps surae in female basketball players.

Static stretch is a safe and feasible method which usually is used before exercise to avoid muscle injury and to improve muscle performance. The purpose of this study was to determine the effects of cyclic static stretch (CSS) on fatigue recovery of triceps surae (TS) in female basketball players. Nine athlete volunteers between 20 and 30 years participated in this study containing two sessions. After warm-up a pressure cuff was fastened above the knee joint and its pressure was increased to 140 mmHg. The subjects were asked to perform one maximum voluntary contraction (MVC) followed by a fatigue test including maximum isometric fatiguing contraction of TS. These steps were similar in both sessions. Then, a two-minute rest was included in the first session while 4 static stretches were performed to TS in the second session. After interventions, one MVC was done and the pressure cuff was released. During these steps, peak torque (PT) and electromyography (EMG) were recorded. The amount of lower leg pain was determined by the visual analogue scale (VAS). The value of PT increased significantly after CSS but its increase was not significant after rest. It seems that the effects of rest and CSS on the EMG parameters, PT and pain are similar.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

Modulation of the ipsilateral and contralateral H reflexes following ipsilateral mechanical pressure of the foot in normal subjects.

OBJECTIVE: Mechanoreceptors from the foot sole likely contribute in the reflex regulations. Therefore, it was hypothesized that repetitive low threshold afferents stimulation would have an inhibitory effect on the soleus H-reflexes. METHODS: Sixteen normal subjects voluntarily, participated in the study and were randomly allocated. Subjects were remained in prone position. The Cutaneous Mechanical Pressure (CMP equal to 50% of leg and foot weight) was applied to the ipsilateral lateral and Medial plantar surface by a designed instrument through a square plate (30 x 30 mm). H reflex as an indicator for excitability of motoneurones was bilaterally elicited before and after the application of the CMP. The H-reflex parameters were estimated. RESULTS: Mechanical pressure significantly depressed soleus H-reflex excitability in ipsilateral and contralateral feet in all subjects. CONCLUSION: The demonstration of a decrease in H-reflex excitability as a result of applied pressure to the foot sole suggests that the change in reflex excitability is the result of a common spinal mechanism. The results highlight the modulatory effects that natural stimulation of afferents can have on reflex excitability. SIGNIFICANCE: The placement of a small flat plate, in order to apply pressure to the plantar eminence, may be useful for modulation of muscle tone. In addition, these findings might be useful for reducing spasticity; because spasticity is at least partially caused by hyperexcitability of the motorneuron pool.