AOC removal and accumulation of bacteria in experimental sand filters

Ces dix dernières années, les méthodes permettant de déterminer la concentration des composés organiques assimilables par les bactéries dans de l'eau potable ont suscité de plus en plus d'intérêt envers les possibilités de prévision et de contrôle de la croissance des bactéries pendant le stockage et la distribution. La détermination dite "COA" (carbone organique aisément assimilable) introduite par VAN DER KOOIJ et. al. (1982) a été développée et appliquée dans le but de surveiller les concentrations de COA pendant le traitement, le stockage et la distribution. Sur la base des résultats, il a été établi un critère pour de l'eau potable biologiquement stable (VAN DER KOOIJ et HIJNEN, 1990). Ce critère exerce une influence sur la conception du traitement de l'eau. Ceci étant, il convient de porter davantage d'attention à l'effet des processus de traitement - et plus particulièrement des processus de filtration - sur la concentration de COA.Des expériences de filtration ont été effectuées sur de petits filtres à sable, dans des conditions de laboratoire bien déterminées. L'objectif de ces expériences consistait à déterminer (I) l'élimination du carbon organique aisément assimilable (COA) dans le filtre, pour des concentrations d'eaux affluentes différentes, (II) l'effet produit sur l'engorgement du filtre et (III) la qualité bactériologique du filtrat.De l'acétate a été ajouté à l'eau d'entrée des filtres en tant que modèle de substrat, dans une gamme de concentrations allant de 0,01 à 1 mg/l C. L'eau fournie était de l'eau potable préfiltrée à faible teneur en COA (0,005 mg ac-C eq/l). Au cours du temps de fonctionnement, la concentration de COA ainsi que le nombre de colonies dénombrées dans l'eau ont été contrôlés, de même que la perte de charge de la couche filtrante. A l'expiration du temps de fonctionnement, la concentration de matière bactérienne a été déterminée dans le sable des filtres.Dans les filtres à sable dont le temps de contact du lit vide était de 10 minutes, les concentrations d'acétate (Sac) inférieures ou égales à 0,25 mg/1 C ont été totalement éliminées. La réduction de COA pour les valeurs Sac de 0,5 et de 1,0 mg/l C atteignait 90 %. Il en a été conclu que les processus de filtration biologique peuvent fort bien être appliqués pour l'élimination de composés organiques aisément assimilables, tels l'acétate et l'éthanol qui sont fréquemment utilisés dans les processus d'élimination biologique des nitrates au cours du traitement de l'eau potable.La capacité d'élimination de l'acétate, offerte par les filtres à sable expérimentaux, était élevée par comparaison avec la réduction de COA observée dans le cas des filtres à sable utilisés pour la production d'eau potable à partir d'une eau de surface (VAN DER KOOIJ, 1984). La teneur en COA du filtrat dépassait le critère applicable à l'eau potable biologiquement stable, c'est-à-dire 0,01 mg ac-C eq/l, pour des charges volumique d'acétate (LVac), relevées sur les filtres à sable expérimentaux, supérieures à 1600 mg ac-C/(m3.h). La charge volumique critique en COA des filtres à sable, utilisés dans les installations de traitement citées plus haut, au-dessus de laquelle la teneur en COA du filtrat dépasse de critère, est estimée à environ 100 mg COA-C/(m3.h).Ces résultats indiquent que l'acétate est éliminé plus rapidement qu'une quantité équivalente de composés mesurée par détermination du COA.Par suite de la consommation d'acétate, le nombre de bactéries présentes dans le lit filtrant s'est accru. On a constaté qu'un net rapport linéaire existait entre la concentration d'acétate, d'une part, et le nombre de colonies dénombrées (par boite) sur le sable à la surface du filtre, d'autre part. L'accumulation de bactéries a été observée, même pour une concentration de COA de 0,005 mg ac-C/l, tandis que l'engorgement des filtres se produisait sous une concentration d'acétate de 0,01 mg ac-C/l. Des concentrations accrues de carbone organique ont été mesurées sur le sable, dans les premiers millimètres d'épaisseur du lit filtrant. Les résultats obtenus à la suite d'études sur le terrain, relatives à l'infiltration d'eau dans les puits de recharge, ont montré que, pour des valeurs de COA inférieures à 0,01 mg ac-C eq/l, la durée de processus n'atteignait pas un an, du fait de l'engorgement observé dans le sous-sol. Par conséquent, ta concentration de carbone organique assimilable (COA) dans l'eau utilisée pour l'infiltration doit être inférieure à 0,01 mg ac-C eq/l afin d'éviter l'engorgement biologique. Un niveau de COA similaire a été conseillé pour l'eau potable bioiogiquement stable (VAN DER KOOIJ and HIJNEN, 1990).La consommation d'acétate dans les filtres a eu comme autre conséquence l'accroissement du nombre de colonies hétérotrophes dénombrées dans l'eau, selon un rapport linéaire avec la concentration d'acétate dans l'eau affluente. Le nombre de colonies dénombrées présentes dans le filtrat s'est accru pour atteindre une valeur moyenne de 104 cfu/ml, sous une concentration d'acétate de 0,068 mg ac-C/l (charge volumique d'acétate de 400 mg ac-C/(m3.h)). Au vu de ces résultats, il a été conclu que la charge volumique en COA d'une filtration finale dans une installation de traitement des eaux devrait être limitée, entre autre afin d'éviter le recours à une post-désinfection visant à réduire le nombre de germes hétérotrophes.Using small sand filets under well defined laboratory conditions, filtration experiments were performed with tap water supplemented with acetate. The objective of these experiments was to determine the effect of different acetate concentrations on (i) the removal of easily assimilable organic carbon (AOC) in the filter (ii), the clogging of the tiller and (iii) the bacteriological quality of the filtrate.The results of the experiments revealed that the reduction capacity of biological filtration processes for acetate is relatively high. Acetate removal resulted in an increased microbiological activity in the top layer (< 1cm) of the filter bed and accumulation of bacterial matter was observed at an influent AOC concentration as low as 0.005 mg of ac-C eq/l. Clogging of the filter bed occurred at an influent acetate concentration of 0.01 mg C/l. Based on these observations it was concluded that the AOC concentration of water used for infiltration in recharge wells should be less thon 0.01 mg ac-C eq/l. This level is similar to the level advised for biologically-stable drinking water.A linear relationship was found between the acetate removal in the experimental filters and the colony count in the filtrate. It was recommended that the AOC load in the final filtration process in water treatment therefore should be limited to prevent high colony counts in the filtrate, thus leading to the use of post disinfection

Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10–39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable ‘red face’, eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia with elongation of the rete ridges was observed in four patients, resembling a psoriasiform dermatitis. Additional immunohistochemical stainings revealed increased numbers of plasma cells, histiocytes and T lymphocytes. Interestingly, spongiosis was largely absent in all biopsies. We report on patients with AD treated with dupilumab developing a paradoxical erythema in a head and neck distribution. Both clinically and histopathologically we found a heterogeneous response, which was most suggestive of a drug-induced skin reaction

Early and Sustained Improvements in Symptoms and Quality of Life with Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis:52-Week Results from Two Phase III Randomized Clinical Trials (Measure Up 1 and Measure Up 2)

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018).</p

Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis

Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage

Treat-to-target in dermatology:A scoping review and International Eczema Council survey on the approach in atopic dermatitis

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.</p

Enterovirus specific anti-peptide antibodies

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13