COVID-19 wastewater based epidemiology: long-term monitoring of 10 WWTP in France reveals the importance of the sampling context.

SARS-CoV-2 wastewater-based epidemiology (WBE) has been advanced as a relevant indicator of distribution of COVID-19 in communities, supporting classical testing and tracing epidemiological approaches. An extensive sampling campaign, including ten municipal wastewater treatment plants, has been conducted in different cities of France over a 20-week period, encompassing the second peak of COVID-19 outbreak in France. A well-recognised ultrafiltration - RNA extraction - RT-qPCR protocol was used and qualified, showing 5.5 +/- 0.5% recovery yield on heat-inactivated SARS-CoV-2. Importantly the whole, solid and liquid, fraction of wastewater was used for virus concentration in this study. Campaign results showed medium- to strong- correlation between SARS-CoV-2 WBE data and COVID-19 prevalence. To go further, statistical relationships between WWTP inlet flow rate and rainfall were studied and taken into account for each WWTP in order to calculate contextualized SARS-CoV-2 loads. This metric presented improved correlation strengths with COVID-19 prevalence for WWTP particularly submitted and sensitive to rain. Such findings highlighted that SARS-CoV-2 WBE data ultimately require to be contextualized for relevant interpretation.

Involvement of neuronal nitric oxide synthase (nNOS) in the regulation of migrating motor complex (MMC) in sheep.

The objectives of this study were to evaluate the role of nitric oxide (NO) synthase isoforms (nNOS, eNOS, and iNOS) in the regulation of the migrating motor complex (MMC) in sheep using electromyography and their expression in the gastrointestinal (GI) tract by Western blot (WB) and immunohistochemistry. Intravenous administration of L-NAME or the nNOS inhibitor 7-nitroindazole (7-NI) decreased the MMC interval. Myoelectric activity of intestinal phase II was increased, whereas antral activity was reduced. These effects were blocked by L-arginine. Inhibitors of either iNOS (aminoguanidine and S-methylisothiourea) or eNOS (L-NIO) were ineffective. The NO donor sodium nitroprusside decreased GI myoelectric activity, inhibited the MMC pattern, and prevented the effects induced by L-NAME and 7-NI in the intestine. Intracerebroventricular administration of these agents did not modify GI motility. In the rumen, abomasal antrum, duodenum, and jejunum, WB showed three bands at about 155, 145, and 135kDa corresponding to nNOS, and a 140-kDa band (eNOS); however iNOS was not detected. Positive nNOS immunostaining was observed in neurons of the myenteric and submucous plexus of all GI tissues, while eNOS was found in the endothelial cells, ruminal and intestinal epithelium, as well as in some enteric neurons and in endocrine-like cells of the duodenal Brunner's glands. In contrast, only weak iNOS immunoreactivity was found in ruminal epithelium. Taken together, our results suggest that NO, synthesized at a peripheral level by nNOS, is tonically inhibiting the MMC pattern and intestinal motility in sheep.

Comparison of two filtration-elution procedures to improve the standard methods ISO 10705-1 & 2 for bacteriophage detection in groundwater, surface water and finished water samples.

AIM: To select a reliable method for bacteriophage concentration prior detection by culture from surface water, groundwater and drinking water to enhance the sensitivity of the standard methods ISO 10705-1 & 2. METHODS AND RESULTS: Artificially contaminated (groundwater and drinking water) and naturally contaminated (surface water) 1-litre samples were processed for bacteriophages detection. The spiked samples were inoculated with about 150 PFU of F-specific RNA bacteriophages and somatic coliphages using wastewater. Bacteriophage detection in the water samples was achieved using the standard method without and with a concentration step (electropositive Anodisc membrane or a pretreated electronegative Micro Filtration membrane, MF). For artificially contaminated matrices (drinking and ground waters), recovery rates using the concentration step were superior to 70% whilst analyses without concentration step mainly led to false negative results. Besides, the MF membrane presented higher performances compared with the Anodisc membrane. CONCLUSION: The concentration of a large volume of water (up to one litre) on a filter membrane avoids false negative results obtained by direct analysis as it allows detecting low number of bacteriophages in water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The addition of concentration step before applying the standard method could be useful to enhance the reliability of bacteriophages monitoring in water samples as bio-indicators to highlight faecal pollution.

Herramientas para mejorar la adherencia al tratamiento con inmunomoduladores en pacientes con esclerosis múltiple / Proposals to improve adherence to immunomodulatory therapies in patients with multiple sclerosis

Introducción: El objetivo de este trabajo fue evaluar los factores, identificados en el estudio global de adherencia (GAP), asociados con la adherencia a los fármacos inmunomoduladores (IMA) en pacientes con esclerosis múltiple (EM) para proponer medidas directas que mejoren la adherencia. Se propuso elaborar cuestionarios que permitiesen detectar, previamente y durante el seguimiento, a pacientes en riesgo de falta de adherencia.Métodos: Se celebraron dos reuniones con investigadores participantes en el estudio GAP en España. Se agruparon factores relacionados con la no adherencia asociados al tratamiento, paciente, enfermedad y profesionales de la salud. Se formaron 4 grupos de trabajo. Cada grupo trabajó de forma individual sobre un factor teniendo en cuenta el diagnóstico de la EM, manejo y aplicación de la medicación, seguimiento y retirada o cambio de tratamiento. Se acordó un borrador de propuestas y herramientas (cuestionarios).Resultados: Se debe proporcionar a los pacientes un resumen de las características de los tratamientos, de modo positivo y simple, así como tiempo para plantear dudas. La entrega de cuestionarios a los pacientes al inicio del tratamiento y durante el seguimiento para evaluar características individuales puede ayudar a conocer su grado de adherencia y actuar en consecuencia. Los pacientes deben ser educados en la identificación y el manejo de las reacciones adversas. Conclusiones: Se recomienda la educación terapéutica para favorecer la adherencia a los tratamientos e identificar a los pacientes no adherentes. Proponemos 2 cuestionarios, de inicio y de seguimiento, para poder estratificar a los pacientes en función de su adherencia (AU)

Introduction: The objective of this work was to assess the factors identified in the Global Adherence Project (GAP) in disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) and to propose measures directed at improving adherence. It was proposed to prepare questionnaires to detect patients at risk of non-adherence before and during the follow-up. Methods: Two meetings were held by Spanish researchers involved in the GAP project. Factors associated with non-adherence were grouped in therapy-, patient-, disease- and health care professional-related factors. Four working groups were created. Each group studied one individual,factor, taking into account the stages of diagnosis, management and administering treatment, follow-up and discontinuation or change of treatment. A draft of proposals and tools (questionnaires) was agreed.Results: Patients should be provided with summaries of treatments, in a positive and simple way, and have time to discuss any doubts. Questionnaires should be given to patients at the start of treatment and during follow-up, so that individual characteristics can be assessed in order to monitor their adherence and act accordingly. Patients should be instructed in the management of the most common adverse reactions. Conclusion:Therapeutic education to improve adherence to treatments and identification of non-adherent patients is recommended. We propose 2 questionnaires, initial and follow up, to stratify patients depending on their adherence (AU)

[Proposals to improve adherence to immunomodulatory therapies in patients with multiple sclerosis]. / Herramientas para mejorar la adherencia al tratamiento con inmunomoduladores en pacientes con esclerosis múltiple.

INTRODUCTION: The objective of this work was to assess the factors identified in the Global Adherence Project (GAP) in disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) and to propose measures directed at improving adherence. It was proposed to prepare questionnaires to detect patients at risk of non-adherence before and during the follow-up. METHODS: Two meetings were held by Spanish researchers involved in the GAP project. Factors associated with non-adherence were grouped in therapy-, patient-, disease- and health care professional-related factors. Four working groups were created. Each group studied one individual,factor, taking into account the stages of diagnosis, management and administering treatment, follow-up and discontinuation or change of treatment. A draft of proposals and tools (questionnaires) was agreed. RESULTS: Patients should be provided with summaries of treatments, in a positive and simple way, and have time to discuss any doubts. Questionnaires should be given to patients at the start of treatment and during follow-up, so that individual characteristics can be assessed in order to monitor their adherence and act accordingly. Patients should be instructed in the management of the most common adverse reactions. CONCLUSION: Therapeutic education to improve adherence to treatments and identification of non-adherent patients is recommended. We propose 2 questionnaires, initial and follow up, to stratify patients depending on their adherence.

Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain).

OBJECTIVE: To ascertain the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Catalonia (autonomous region in northeast Spain), examined according to the currently established disease subtypes. METHODS: Before initiating the study, we conducted an educational programme on paediatric rheumatology, addressed to all general paediatricians in Catalonia. A 2-year (2004-2006), prospective, population-based study was then carried out to determine the incidence of JIA. Prospective and retrospective data retrieval was performed to calculate prevalence. The International League of Associations for Rheumatology (ILAR, Edmonton revision) classification criteria were applied. RESULTS: Over the study period, 145 new cases of JIA were diagnosed. The mean annual incidence was 6.9/105 children aged less than 16 years (range 5.8-8.1 years; 9.0 years for girls and 4.8 years for boys). On separate analysis of patients ≤ 6 and > 6 years, the distribution in younger children was found to be similar for both girls and boys, whereas in older children, most girls belonged to the oligoarthritis and polyarthritis subgroups, and boys to the enthesitis-related arthritis and undifferentiated subgroups. The calculated prevalence of JIA (31 October 2006) was 39.7 (36.1-43.7)/105 children younger than 16. The relative risk of girls having JIA was 2.1 [95% confidence interval (CI) 1.7-2.7, p < 0.001]. In 70% of patients, the diagnosis was established before the age of 7. Subgroup distribution of prevalent cases mirrored that of incident cases. CONCLUSION: This is the first population-based study on the epidemiology of JIA in Catalonia. Incidence and prevalence rates are lower than those reported for several areas in Nordic countries of Europe. Oligoarthritis was the most common subtype.

Adenovirus, MS2 and PhiX174 interactions with drinking water biofilms developed on PVC, cement and cast iron.

Biofilms colonizing pipe surfaces of drinking water distribution systems could provide habitat and shelter for pathogenic viruses present in the water phase. This study aims (i) to develop a method to detect viral particles present in a drinking water biofilm and (ii) to study viral interactions with drinking water biofilms. A pilot scale system was used to develop drinking water biofilms on 3 materials (7 cm(2) discs): PVC, cast iron and cement. Biofilms were inoculated with viral model including MS2, PhiX174 or adenovirus. Five techniques were tested to recover virus from biofilms. The most efficient uses beef extract and glycine at pH = 9. After sonication and centrifugation, the pH of the supernatant is neutralized prior to viral analysis. The calculated recovery rates varied from 29.3 to 74.6% depending on the virus (MS2 or PhiX174) and the material. Applying this protocol, the interactions of virus models (MS2 and adenovirus) with drinking water biofilms were compared. Our results show that adsorption of viruses to biofilms depends on their isoelectric points, the disc material and the hydrodynamic conditions. Applying hydrodynamic conditions similar to those existing in drinking water networks resulted in a viral adsorption corresponding to less than 1% of the initial viral load.

Papel de la ciclooxigenasa (COX) en las alteraciones motoras gastrointestinales y la fiebre inducidas por el lipopolisacárido (LPS) en la oveja / No disponible

No disponible

Multiple sclerosis association study with the TENR-IL2-IL21 region in a Spanish population.

Polymorphisms from the TENR-IL2-IL21 block in the 4q27 chromosome were recently associated with type 1 diabetes, celiac disease, rheumatoid arthritis and psoriasis. We undertook this study to investigate the potential role of polymorphisms rs3136534, rs6822844 and rs2069762 (-330 T/G IL2) in multiple sclerosis (MS) (805 patients of Spanish Caucasian origin and 952 health controls). We did not find evidence for association with any single nucleotide polymorphisms (SNPs) tested. Allele and genotype frequencies of the SNPs, which were studied, were similar in DRB1*15-positive or DRB1*15-negative patients. After stratification of MS patients by clinical course, a weak association was observed with rs2069762 G allele and haplotype bearing this allele with secondary progressive MS, although these cases represent 22% of the MS cases. Our results did not show major influence of TENR-IL2-IL21 locus on susceptibility or disease progression in MS. However, we could not exclude completely the effect in MS for this region. Additional studies, using much larger sample sizes and analysis of additional polymorphisms in the gene and its flanking region, will be required to ascertain their contributions to MS susceptibility.

The T244I variant of the interleukin-7 receptor-alpha gene and multiple sclerosis.

Several but not all studies have provided evidence for the association between multiple sclerosis (MS) and the T244I variant of the interleukin-7 receptor-alpha gene (IL7RA), rs6897932. We performed a new replication case-control study in 599 MS patients and 594 healthy controls, all Caucasians from the south of Spain. The genotype and allele frequencies differed between MS cases and controls. The IL7RA rs6897932 C allele and the CC genotype were found to be factors for disease susceptibility [per allele odds ratio (OR) 1.32, 95% CI 1.1-1.6, P=0.0031; per CC genotype vs TT + TC genotypes, OR 1.5, 95% CI 1.18-1.87, P=0.0007]. The combined data analysis included 3324 cases and 5032 controls of Europeans and Americans of European origin resulting in stronger association with similar OR (P=1.9 x 10E-9). These findings in our sample support previous reported association studies between IL7RA rs6897932 and MS.

Multiple sclerosis in Gypsies from southern Spain: prevalence, mitochondrial DNA haplogroups and HLA class II association.

Occasional reports have mentioned the prevalence of multiple sclerosis (MS) among Gypsies, and no studies have examined to date the prevalence of MS or human leukocyte antigen (HLA) genetics associations in the Spanish Gypsy population. We decided to study the prevalence, mitochondrial DNA (mtDNA) haplogroups and HLA class II distribution among gypsies with MS in southern Spain. We searched for Gypsy MS patients and studied HLA class II alleles by polymerase chain reaction with sequence-specific oligonucleotide (PCR/SSO) probe hybridization or sequence-specific primers amplification. An additional study of the mtDNA haplogroups by sequencing of the hypervariable segments of the control region was also performed to provide details of their ethnic origin. Estimated prevalence of MS in the Gypsy population in Malaga was 52/100,000. No significant differences were found in mtDNA between Gypsy MS patients and Gypsy controls. DRB1*1501, DQB1*0602 and DQB1*0608 alleles were the only positive HLA association with MS. The Gypsies in our series have the same anthropological origin as other European gypsy groups, as shown by mtDNA haplogroups. Although interpreted with great caution because of the small sample size, we found that the prevalence of MS in Gypsies in Malaga is not as low as that in Central Europe, although it is significantly less than that found in Caucasians from Spain (75-79/100,000). DQB1*0602 was the strongest positive association found with Gypsy MS patients, and DRB1*1501-DQB1*0602 was the most frequent haplotype in this group.

Phylogenetic relationships and evolution of cleaning behaviour in the family Labridae: importance of body colour pattern.

The family Labridae contains numerous fishes known to act as cleaners in the wild. Previous studies suggested that a small body size and specific colour patterns may be prerequisites for cleaning. We investigated whether cleaning behaviour is linked to particular fish phenotypes. We first present a phylogeny based on partial 12S rRNA gene sequences of 32 wrasses sampled from different localities in the Indo-Pacific and Atlantic oceans, and in the Mediterranean Sea. Secondly, descriptive data (fish body size, fish body shape and fish body colour patterns) were analyzed in a phylogenetic context using comparative methods. We found no relationship between fish cleaning behaviour and fish body size and shape, but instead a correlation between cleaning behaviour and the presence of a dark lateral stripe within wrasses. Our results suggest that the evolution of cleaning depends upon the presence of a dark median lateral stripe on the fish body surface.

Animales de experimentación utilizados como modelos en la investigación de la arteriosclerosis / Experimental animals used as models in arteriosclerosis research

La presente revisión aborda el metabolismo lipoproteico comparado y la inducción de la aterosclerosis con sus controversias en varios modelos animales pertenecientes a un amplio espectro evolutivo que abarca desde los roedores (ratón, conejo, rata, hámster, cobaya), las aves (paloma), los cetartiodáctilos (cerdo) y los carnívoros (perro) hasta los primates (macacos, Rhesus, mono verde africano) (AU)

Current review presents an overview of the compared lipoprotein metabolism and atherosclerosis development and their controversies in several animal models covering a wide phylogenetic spectrum. Orders are rodents (mice, rabbits, rats, hamsters, guinea pigs), birds (pigeons), cetartiodactyla (pigs), carnivores (dogs) and primates (macaques, Rhesus, African green monkey) (AU)

Assessing the cost of groundwater pollution: the case of diffuse agricultural pollution in the Upper Rhine valley aquifer.

This paper presents an assessment of the costs of diffuse groundwater pollution by nitrates and pesticides for the industrial and the drinking water sectors in the Upper Rhine valley, France. Pollution costs which occurred between 1988 and 2002 are described and assessed using the avoidance cost method. Geo-statistical methods (kriging) are then used to construct three scenarios of nitrate concentration evolution. The economic consequences of each scenario are then assessed. The estimates obtained are compared with the results of a contingent valuation study carried out in the same study area ten years earlier.

TNF-alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis.

OBJECTIVE: To explore the possible association/s of the first reported tumour necrosis factor (TNF-alphaTNF-) alpha promoter gene polymorphisms -308, -238, -376 and -163 (G-->A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population. METHODS: The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR). TNF-alpha promoter gene polymorphisms were screened using PCR denaturing gradient gel electrophoresis (PCR-DGGE), followed, if positive, by restriction fragment length polymorphism (RFLP) analysis for identification. RESULTS: No statistical association was found between the four polymorphisms studied and JIA. However, the -308 G-->A polymorphism (TNF A2) tended to be more frequent in patients with SoJIA than in the oligoarticular group. TNF A2 was strongly associated with the extended haplotype A1B8DR3 (p = 0.003), and the tandem polymorphism -238/-376 in the presence of B18 and DR3. CONCLUSION: The TNF A2 allele was more frequent in SoJIA than in the oligoarticular group. TNF A2 can help to create a more inflammatory milieu in this JIA subtype, in combination with other polymorphisms involved in regulatory sequences of key molecules in the inflammatory response. The association of the -308 and -238/-376 polymorphisms with specific alleles of the HLA is reconfirmed.

Respuesta de los autores: El síndrome de Schnitzler / No disponible

No disponible

Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis.

OBJECTIVE: To explore all the common clinical and biological variables that are characteristic of Systemic onset Juvenile Chronic Arthritis (SoJCA) in order to determine which of them are suitable as predictors of a bad articular outcome (persistence of inflammatory symptoms and/or established limitation of the range of motion (ROM). MATERIAL AND METHODS: Clinical charts for 124 SoJCA patients were retrospectively reviewed. From them, 91 were finally included in the study because they had all of the clinical and biological data at disease onset properly recorded. All have been followed for at least 3 years since the beginning of the disease. Data collected at onset, and after 3 and 6 months of the disease included: 1) systemic symptoms; 2) joint involvement, using both the usual articular count and the value of an articular index (Helsinki Index = HI) which intentionally excludes those joints that are not uniformly recorded in clinical charts; and 3) biological data. HI was used to separate the patients into two groups. When applied 3 years after the disease onset, HI > or = 10 represented a bad articular outcome while HI < 10 meant a good prognosis. SPSS for Windows 6.1 was used for both the univariate and multivariate analyses. RESULTS: From the multivariate logistic regression analysis, two different "clusters" of clinical data were found to be the best predictors of a bad articular outcome. A bad prognosis was linked at onset with the presence of generalized lymphadenopathies, age < 8 years and an HI > 6; at six months a bad outcome was linked with the presence of a polyarticular pattern plus hip involvement. CONCLUSION: Clinical parameters at the beginning of the disease were shown to be extremely useful in predicting the articular outcome of SoJCA. Therefore, they could constitute a good instrument to help clinicians tailor the best therapy for their patients.

[Infective endocarditis related to pacemaker leads. A review]. / Les endocardites infectieuses sur sondes de pacemaker.

Infective endocarditis is a rare but serious complication of permanent cardiac pacing with high mortality ranging from 10 to 30%. Clinical symptoms are sometimes acute but more often poor and aspecific in subacute and chronic forms causing prolonged diagnostic delay. In order to make endocarditis on pacemaker leads clearer, we conducted a medline search of all published literature. Analysis of this literature shows that the initial infective source is often local and that Staphylococcus species are the most often pathogens isolated. Clinicians have to search carefully for local inflammatory signs, past or ongoing, and pulmonary embolism because their presence will be helpful for diagnosis. Transoesophageal echocardiography is essential; it shows vegetations in more than 90% and must be repeated when the examination is negative. Treatment has a double goal: a prophylactic treatment in order to reduce risk factors of infection related to implantation of the pacemaker and a curative treatment associating prolonged antibiotic therapy with extraction of the material.

Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis. A puzzle illustrated by a new case.

We report a case of amyotrophic lateral sclerosis in a patient with rheumatoid arthritis. Only three similar cases have been reported. Our case illustrates the diagnostic difficulties raised by early amyotrophic lateral sclerosis responsible for localized or unusual manifestations. Occurrence of the two diseases in the same patient is probably due to chance alone.

Nocardia infection of a joint prosthesis complicating systemic lupus erythematosus.

The authors report the case of a 43-year-old woman suffering from severe systemic lupus erythematosus treated with long-term prednisone, who developed Nocardia nova infection on a hip prosthesis. Sepsis occurred about two years after an episode of pulmonary nocardiosis with the same Nocardia species, that was successfully treated by 12 months of antibiotics. A good outcome of the joint infection was observed in response to antibiotics and removal of the prosthesis. Nocardiosis is a rare infection, acting as an opportunistic infection, facilitated in the present case by systemic lupus erythematosus and chronic corticosteroid therapy. Nocardia infections mainly affect the lungs, skin and central nervous system; these last two sites are mostly due to haematogenous spread, a frequent event. Treatment is based on antibiotics, usually continued for 3-12 months, especially because of the risk of relapse. The imipenem-amikacin combination appears to be more effective than trimethoprim sulfamethoxazole. To our knowledge, this is the first case report of Nocardia nova joint prosthesis infection also presenting as late septic spread of pulmonary nocardiosis, complicating corticosteroid-treated systemic lupus erythematosus.