Genome sequencing identify chromosome 9 inversions disrupting ENG in 2 unrelated HHT families.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the ENG and ACVRL1 genes are responsible for most cases of HHT. Four families with a negative targeted gene panel and selected by a multidisciplinary team were selected and whole-genome sequencing was performed according to the recommendations of the French National Plan for Genomic Medicine. Structural variations were confirmed by standard molecular cytogenetic analysis (FISH). In two families with a definite diagnosis of HHT, we identified two different paracentric inversions of chromosome 9, both disrupting the ENG gene. These inversions are considered as pathogenic and causative for the HHT phenotype of the patients. This is the first time structural variations are reported to cause HHT. As such balanced events are often missed by exon-based sequencing (panel, exome), structural variations may be an under-recognized cause of HHT. Genome sequencing for the detection of these events could be suggested for patients with a definite diagnosis of HHT and in whom no causative pathogenic variant was identified.

[Messages from the estates general on French internal medicine]. / Que retenir des états généraux de la médecine interne française ?

Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice.

Serum ferritin/C-reactive protein ratio is a simple and effective biomarker for diagnosing iron deficiency in the context of systemic inflammation.

BACKGROUND: Diagnosing iron deficiency is challenging in the presence of systemic inflammation. AIM: To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome. DESIGN: Test prospective cohort and validation retrospective cohort. METHODS: A prospective cohort of inpatients (n = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n = 795) further assessed the predictive power of this ratio. RESULTS: In a training cohort (median age 76 years [57-84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57-84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85-0.90], with an odds ratio of 37.9 [95% CI: 20.3-68.9] for the threshold of ≤6. CONCLUSION: In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies.

[Characteristics of patients with connective tissue disease-associated pulmonary arterial hypertension treated with prostanoids: A multicenter retrospective study]. / Caractéristiques des patients traités par prostanoïdes pour une hypertension artérielle pulmonaire associée à une connectivite : étude multicentrique rétrospective.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment. METHODS: In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment. RESULTS: Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment. CONCLUSION: This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

Agroecology landscapes.

Context: Agroecology combines agronomic and ecological concepts. It relies on the enhancement of biodiversity and related ecosystem services to support agricultural production. It is dependent on biological interactions for the design and management of agricultural systems in agricultural landscapes. Objectives: We review the role of landscape ecology to understand and promote biodiversity, pest regulation and crop pollination for the designing of "agroecology landscapes". We illustrate the use of landscape ecological methods for supporting agroforestry systems as an example of agroecological development, and we propose pathways to implement agroecology at landscape scale. Methods: The state of the art of how landscape ecology contributes to agroecology development is summarized based on a literature review. Results: Agroecology requires thinking beyond the field scale to consider the positioning, quality and connectivity of fields and semi-natural habitats at larger spatial scales. The spatial and temporal organisation of semi-natural elements and the crop mosaic interact. Understanding this interaction is the pre-requisite for promoting patterns and mechanisms that foster biodiversity and ecosystem service provision. Promoting agroecological practices beyond individual farm borders can be rooted in a bottom-up approach from agroecological lighthouse farms to farm networks to amplify agroecology adoption at the landscape scale. Conclusions: Achieving agricultural landscapes composed of fields and farms following agroecological management requires understanding of biodiversity patterns, biological interactions and mechanisms that determine and boost ecosystem functioning to improve services at landscape scale, involving farmers in a bottom-up and context-specific approach.

[Which adjuvant measures should be associated with long-term oral corticosteroid therapy in inflammatory diseases? A summary of existing French recommendations]. / Quelles mesures adjuvantes associer à une corticothérapie orale prolongée dans le cadre des maladies inflammatoires ? Synthèse des recommandations françaises disponibles.

It is common to initiate a long-term corticosteroid therapy for inflammatory diseases. Various specialists are involved in this prescription, and associated measures to prevent side effects are not consensual, with the exception of osteoporosis. The specialty of the prescriber has indeed a significant impact on the attention paid to the adjuvant associated measures. The aim of this review was to draw a summary of the side effects of long-term corticosteroid therapy and of the existing recommendations related to associated measures to prevent them. Unfortunately, it is difficult to give clear recommendations because of the lack of evidence in some fields, especially as they should be adapted to patient's age and comorbidities. We propose a summary table of associated measures to long-term steroid therapy prescription and suggest a monitoring frequency.

Assessing the environmental performance for more local and more circular biowaste management options at city-region level.

Biomass, biobased materials and food waste are considered priority areas for Europe's transition towards a circular economy (CE). Waste management is a central activity for this transition and offers multiple CE implementation options which should be evaluated from environmental perspective. The purpose of this work was to analyze the environmental consequences when redirecting biowaste flows from conventional to more circular management systems and to identify the CE option with the best environmental performance. We were particularly interested in studying the combined management of green and food waste, analyzing the challenges when introducing separate collection and different treatment processes, and evaluating the substitution potential for by-products. To determine environmental impacts, we performed a life cycle assessment (LCA) based on local data. Following the purpose analyzing a change in the system, we applied a consequential LCA and compared impacts from processes that are replaced with impacts from alternative management options such as co-composting, anaerobic digestion (AD) and decentralized composting. The LCA results show clear advantages for impacts on ecosystems and resource use for the local AD system with separate combined collection. The decentralized system shows reductions in resource use, whereas the industrial co-composting system has higher or similar impacts than the baseline scenario. We conclude that local systems with combined food and green waste management can show benefits if process emissions are properly managed and if by-products are used in applications with high substitution potentials. However, a change towards a CE does not necessarily result in environmental benefits. Our research highlights the complexity of biowaste systems and proposes a novel combination of local data, databases and models to handle this issue. With this research we are further contributing to the understanding of the combined management of food and green waste, which is a relevant, but so far under-researched, management option for cities.

Bone lesions in systemic mastocytosis: Bone histomorphometry and histopathological mechanisms.

Osteoporosis is considered the most frequent skeletal manifestation of systemic mastocytosis (SM). We performed a retrospective analysis of sixty patients (37 males and 23 females) who underwent a bone biopsy in the assessment of SM or in the assessment of unexplained bone fragility. Thirty-three had simultaneously a bone marrow biopsy with a Jamshidi's needle; this sample was used for immunohistochemical analysis (tryptase, c-KIT. CD20, VCAM-1). Bone biopsy was realized in 42 cases in the assessment of SM to provide histologic proof of the disease and in 18 cases in the assessment of unexplained bone fragility and surprisingly revealed a SM. An increased bone turnover was observed in patients with SM with elevated eroded surfaces, osteoclast number and bone formation rate. In addition to nodules of mast cells (MC), a high number of MC was directly apposed on the trabeculae, affixed on the osteoblasts or the lining cells. The VCAM-1 adhesion protein recognizing α4ß7 and α4ß1 integrins may be a candidate to explain this particular adherence. One third of the bone marrow biopsies did not exhibit MC nodules or MC infiltration and led to a false negative diagnosis for SM. SM can be discovered in the assessment of fracture or osteoporosis. Transiliac bone biopsy allows for the diagnosis of the disease more accurately than bone marrow biopsy; it also provides a histomorphometric analysis of bone remodeling.

Giant cell arteritis-related aortitis with positive or negative temporal artery biopsy: a French multicentre study.

Objective: To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB).Method: Patients with GCA-related aortitis diagnosed between 2000 and 2017, who underwent TAB, were retrospectively included from a French multicentre database. They all met at least three American College of Rheumatology criteria for the diagnosis of GCA. Aortitis was defined by aortic wall thickening > 2 mm on computed tomography scan and/or an aortic aneurysm, associated with an inflammatory syndrome. Patients were divided into two groups [positive and negative TAB (TAB+, TAB-)], which were compared regarding aortic imaging characteristics and aortic events, at aortitis diagnosis and during follow-up.Results: We included 56 patients with TAB+ (70%) and 24 with TAB- (30%). At aortitis diagnosis, patients with TAB- were significantly younger than those with TAB+ (67.7 ± 9 vs 72.3 ± 7 years, p = 0.022). Initial clinical signs of GCA, inflammatory parameters, and glucocorticoid therapy were similar in both groups. Coronary artery disease and/or lower limb peripheral arterial disease was more frequent in TAB- patients (25% vs 5.3%, p = 0.018). Aortic wall thickness and type of aortic involvement were not significantly different between groups. Diffuse arterial involvement from the aortic arch was more frequent in TAB- patients (29.1 vs 8.9%, p = 0.03). There were no differences between the groups regarding overall, aneurism-free, relapse-free, and aortic event-free survival.Conclusion: Among patients with GCA-related aortitis, those with TAB- are characterized by younger age and increased frequency of diffuse arterial involvement from the aortic arch compared to those with TAB+, without significant differences in terms of prognosis.

[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

Faunistic analyses of fruit fly species (Diptera: Tephritidae) in orchards surrounded by Atlantic Forest fragments in the metropolitan region of Curitiba, Paraná state, Brazil / Análise faunística de moscas-das-frutas (Diptera: Tephritidae) em pomares rodeados por fragmentos da Mata Atlântica na região metropolitana de Curitiba, Paraná, Brasil

Abstract The objective of this trial was to characterize the assemblage structure of fruit flies (Diptera: Tephritidae) by determining the diversity and faunal indices. Fruit flies were collected for ten years between 2003 and 2015 in six municipalities of the Metropolitan Region of Curitiba, Paraná. The orchards were divided into three crop protection strategies: organic, conventional, and integrated pest management. The characteristic of each community was determined using the Shannon-Wiener, Margalef, and Pielou's indexes. The frequency, constancy, and dominance indexes were also determined. Biological material was analyzed using the explanatory variables: site, crop, plant protection strategy, and susceptibility period. A total of 8,089 fruit flies were collected, of which 4,681 were females. The species Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene and A. pickeli Lima were recorded for the first time in Paraná State, the occurrence of three other species was recorded for the first time in the Metropolitan Region of Curitiba (A. montei Lima, A. obliqua Macquart, and A. sororcula Zucchi), in addition A. fraterculus (Wiedemann), A. grandis (Macquart) and Ceratitis capitata (Wiedemann). A. fraterculus accounted for 98.5% of the collected species. Only A. fraterculus and A. sororcula were found in fruits. Fruit flies occurred predominantly in peach trees cultivated under organic conditions. The Shannon index indicated that the municipality of Cerro Azul had the highest diversity and richness whereas apple orchards had the lowest diversity. Crops cultivated under organic conditions exhibited the highest diversity whereas those cultivated under conventional conditions had the highest evenness index. The largest specimens number was collected during the period of crop susceptibility.

Resumo O objetivo deste estudo foi caracterizar agrupamento de espécies de moscas-das-frutas (Diptera: Tephritidae) pela determinação da diversidade e dos índices faunísticos. As moscas-das-frutas foram coletadas por dez anos entre 2003 e 2015 em seis municípios da Região Metropolitana de Curitiba, no Paraná. Os pomares foram divididos em três estratégias de proteção de culturas: orgânica, convencional e integrada. A característica de cada comunidade foi determinada usando os índices de Shannon-Wiener, Margalef e Pielou. Os índices de freqüência, constância e dominância também foram determinados. O material biológico foi analisado utilizando as variáveis explicativas: local, cultura, estratégia de proteção e período de susceptibilidade. Foram coletadas 8.089 moscas-das-frutas, sendo 4.681 fêmeas. As espécies Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene e A. pickeli Lima foram registradas pela primeira vez no Estado do Paraná, e pela primeira vez, na Região Metropolitana de Curitiba, as espécies A. montei Lima, A. obliqua Macquart e A. sororcula Zucchi), além de A. fraterculus (Wiedemann), A. grandis (Macquart) e Ceratitis capitata (Wiedemann). A. fraterculus foi responsável por 98,5% das espécies coletadas. Apenas A. fraterculus e A. sororcula foram encontrados em frutos. As moscas-das-frutas ocorreram predominantemente em pessegueiros cultivados sob condições orgânicas. O índice de Shannon indicou que o município de Cerro Azul teve a maior diversidade e riqueza, enquanto que a cultura macieira teve a menor diversidade. As culturas sob condição orgânica exibiram a maior diversidade, enquanto as cultivadas em condições convencionais apresentaram o maior índice de uniformidade. O maior número de espécimes foi coletado durante o período de suscetibilidade à cultura.

Local pesticide use intensity conditions landscape effects on biological pest control.

Complex landscapes including semi-natural habitats are expected to favour natural enemies thereby enhancing natural pest biocontrol in crops. However, when considering a large number of situations, the response of natural biocontrol to landscape properties is globally inconsistent, a possible explanation being that local agricultural practices counteract landscape effects. In this study, along a crossed gradient of pesticide use intensity and landscape simplification, we analysed the interactive effects of landscape characteristics and local pesticide use intensity on natural biocontrol. During 3 years, using a set of sentinel prey (weed seeds, aphids and Lepidoptera eggs), biocontrol was estimated in 80 commercial fields located in four contrasted regions in France. For all types of prey excepted weed seeds, the predation rate was influenced by interactions between landscape characteristics and local pesticide use intensity. Proportion of meadow and length of interface between woods and crops had a positive effect on biocontrol of aphids where local pesticide use intensity was low but had a negative effect elsewhere. Moreover, the landscape proportion of suitable habitats for crop pests decreased the predation of sentinel prey, irrespectively of the local pesticide use intensity for weed seeds, but only in fields with low pesticide use for Lepidoptera eggs. These results show that high local pesticide use can counteract the positive expected effects of semi-natural habitats, but also that the necessary pesticide use reduction should be associated with semi-natural habitat enhancement to guarantee an effective natural biocontrol.

[Treatment of ITP and AIHA in CVID: A systematic literature review]. / Traitement du PTI et de l'AHAI au cours du DICV : revue systématique de la littérature.

INTRODUCTION: Ten to 15% of common variable immunodeficiencies (CVID) develop auto-immune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Treatment is based on immunosuppressants, which produce blocking effects in the CVID. Our objective was to assess their risk-benefit ratio in these immunocompromised patients. METHODS: We identified 17 articles detailing the treatment of AIHA and/or ITP in patients suffering from CVID through a systematic review of the MEDLINE database. RESULTS: The increased infectious risk with corticosteroids does not call into question their place in the first line of treatment of ITP and AIHA in CVID. High-doses immunoglobulin therapy remain reserved for ITP with a high risk of bleeding. In second-line treatment, rituximab appears to be effective, with a lower infectious risk than the splenectomy. Immunosuppressants (azathioprine, methotrexate, mycophenolate, cyclophosphamide, vincristine, ciclosporine) are moderately effective and often lead to severe infections, meaning that their use is justified only in resistant cases and steroid-sparing. Dapsone, danazol and anti-D immunoglobulins have an unfavorable risk-benefit ratio. The place of TPO receptor agonists is still to be defined. The establishment of immunoglobulin replacement in the place of immunosuppressants (except for short-term corticotherapy) or splenectomy appears to be essential to limit the risk of infections, including in the absence of previous infections. CONCLUSION: The presence of CVID does not mean that it is necessary to give up on corticosteroids as a first-line treatment and rituximab as a second-line treatment for AIHA and ITP, but it should be in addition to immunoglobulin replacement. A splenectomy should be reserved as a third-line treatment.

[Chronic superficial urticaria associated with solid cancers: Case report and literature review]. / Urticaire chronique superficielle associée aux cancers solides : un cas et revue de la littérature.

BACKGROUND: Chronic urticaria is common and is generally idiopathic ("spontaneous"). Links between solid cancer and chronic urticaria have been mentioned in the literature. PATIENTS AND METHODS: We report the case of a 63-year-old man presenting with superficial chronic urticaria associated with adenocarcinoma of the ethmoid sinus. We discuss the possibility of systemic origin in light of the severity of the disease and its resistance to treatment. Only recurrent ethmoidal cancer was highlighted. Curative care resulted in complete resolution of the urticaria without relapse at 32 months of follow-up. DISCUSSION: In a literature review, we collected 17 cases of superficial chronic urticaria associated with cancer. These cases were marked by synchronous progression and by the inefficacy (86%) of anti-histamines and systemic corticosteroids. Although cases of chronic superficial urticaria associated with cancer remain rare, the condition merits discussion due to its severity and significant resistance to therapy.

Faunistic analyses of fruit fly species (Diptera: Tephritidae) in orchards surrounded by Atlantic Forest fragments in the metropolitan region of Curitiba, Paraná state, Brazil.

The objective of this trial was to characterize the assemblage structure of fruit flies (Diptera: Tephritidae) by determining the diversity and faunal indices. Fruit flies were collected for ten years between 2003 and 2015 in six municipalities of the Metropolitan Region of Curitiba, Paraná. The orchards were divided into three crop protection strategies: organic, conventional, and integrated pest management. The characteristic of each community was determined using the Shannon-Wiener, Margalef, and Pielou's indexes. The frequency, constancy, and dominance indexes were also determined. Biological material was analyzed using the explanatory variables: site, crop, plant protection strategy, and susceptibility period. A total of 8,089 fruit flies were collected, of which 4,681 were females. The species Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene and A. pickeli Lima were recorded for the first time in Paraná State, the occurrence of three other species was recorded for the first time in the Metropolitan Region of Curitiba (A. montei Lima, A. obliqua Macquart, and A. sororcula Zucchi), in addition A. fraterculus (Wiedemann), A. grandis (Macquart) and Ceratitis capitata (Wiedemann). A. fraterculus accounted for 98.5% of the collected species. Only A. fraterculus and A. sororcula were found in fruits. Fruit flies occurred predominantly in peach trees cultivated under organic conditions. The Shannon index indicated that the municipality of Cerro Azul had the highest diversity and richness whereas apple orchards had the lowest diversity. Crops cultivated under organic conditions exhibited the highest diversity whereas those cultivated under conventional conditions had the highest evenness index. The largest specimens number was collected during the period of crop susceptibility.

[Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A retrospective multicentric study of 28 adult cases]. / Déficit en sphingomyélinase acide (maladie de Niemann-Pick B) : une étude rétrospective multicentrique de 28 patients adultes.

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.

Faunistic analyses of fruit fly species (Diptera: Tephritidae) in orchards surrounded by Atlantic Forest fragments in the metropolitan region of Curitiba, Paraná state, Brazil

Abstract The objective of this trial was to characterize the assemblage structure of fruit flies (Diptera: Tephritidae) by determining the diversity and faunal indices. Fruit flies were collected for ten years between 2003 and 2015 in six municipalities of the Metropolitan Region of Curitiba, Paraná. The orchards were divided into three crop protection strategies: organic, conventional, and integrated pest management. The characteristic of each community was determined using the Shannon-Wiener, Margalef, and Pielous indexes. The frequency, constancy, and dominance indexes were also determined. Biological material was analyzed using the explanatory variables: site, crop, plant protection strategy, and susceptibility period. A total of 8,089 fruit flies were collected, of which 4,681 were females. The species Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene and A. pickeli Lima were recorded for the first time in Paraná State, the occurrence of three other species was recorded for the first time in the Metropolitan Region of Curitiba (A. montei Lima, A. obliqua Macquart, and A. sororcula Zucchi), in addition A. fraterculus (Wiedemann), A. grandis (Macquart) and Ceratitis capitata (Wiedemann). A. fraterculus accounted for 98.5% of the collected species. Only A. fraterculus and A. sororcula were found in fruits. Fruit flies occurred predominantly in peach trees cultivated under organic conditions. The Shannon index indicated that the municipality of Cerro Azul had the highest diversity and richness whereas apple orchards had the lowest diversity. Crops cultivated under organic conditions exhibited the highest diversity whereas those cultivated under conventional conditions had the highest evenness index. The largest specimens number was collected during the period of crop susceptibility.

Resumo O objetivo deste estudo foi caracterizar agrupamento de espécies de moscas-das-frutas (Diptera: Tephritidae) pela determinação da diversidade e dos índices faunísticos. As moscas-das-frutas foram coletadas por dez anos entre 2003 e 2015 em seis municípios da Região Metropolitana de Curitiba, no Paraná. Os pomares foram divididos em três estratégias de proteção de culturas: orgânica, convencional e integrada. A característica de cada comunidade foi determinada usando os índices de Shannon-Wiener, Margalef e Pielou. Os índices de freqüência, constância e dominância também foram determinados. O material biológico foi analisado utilizando as variáveis explicativas: local, cultura, estratégia de proteção e período de susceptibilidade. Foram coletadas 8.089 moscas-das-frutas, sendo 4.681 fêmeas. As espécies Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene e A. pickeli Lima foram registradas pela primeira vez no Estado do Paraná, e pela primeira vez, na Região Metropolitana de Curitiba, as espécies A. montei Lima, A. obliqua Macquart e A. sororcula Zucchi), além de A. fraterculus (Wiedemann), A. grandis (Macquart) e Ceratitis capitata (Wiedemann). A. fraterculus foi responsável por 98,5% das espécies coletadas. Apenas A. fraterculus e A. sororcula foram encontrados em frutos. As moscas-das-frutas ocorreram predominantemente em pessegueiros cultivados sob condições orgânicas. O índice de Shannon indicou que o município de Cerro Azul teve a maior diversidade e riqueza, enquanto que a cultura macieira teve a menor diversidade. As culturas sob condição orgânica exibiram a maior diversidade, enquanto as cultivadas em condições convencionais apresentaram o maior índice de uniformidade. O maior número de espécimes foi coletado durante o período de suscetibilidade à cultura.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). METHODS: A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. RESULTS: One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. CONCLUSION: In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

Estabilización anterolateral del tobillo por incisión mínima con técnica de hemi-Castaing modificada / Minimal invasive anterolateral ankle stabilization with a modified Hemi-Castaing technique

Antecedentes: Las lesiones de los ligamentos laterales del tobillo son comúnmente observadas en las actividades deportivas. Se encuentran descritas múltiples técnicas para su tratamiento, todas con un último fin: lograr una adecuada estabilidad del tobillo. Las técnicas de invasión mínima y los adelantos tecnológicos en los sistemas de fijación hueso-tendón han venido ganando adeptos en la última década y han impactado también las técnicas de estabilización del tobillo. Material y métodos: Se incluyeron todos los pacientes con diagnóstico de inestabilidad lateral de tobillo que se intervinieron quirúrgicamente y se les realizó un procedimiento de Hemi-Castaing modificado con abordajes mínimos operados en el período de Mayo 2004 a Diciembre del 2007. Tenemos un seguimiento promedio de 30.3 meses. Resultados: Nuestros pacientes presentaron una buena evolución, encontramos una mejoría importante en la escala de Karlsson de 48.7 puntos (± 15.6) a 93.6 puntos (± 9.6). Los pacientes regresaron a su actividad deportiva posterior a la cirugía a los 5.72 meses en promedio (± 4.93). Tenemos una adecuada estabilización corroborada con radiografías dinámicas con sistema Telos. Con una satisfacción personal excelente y buena en 81.9% de los pacientes. Conclusiones: Las modificaciones a la técnica de Hemi-Castaing con el abordaje por incisión mínima, son seguras, reproducibles y nos dan una herramienta más para el tratamiento de esta patología y sobre todo en los casos en donde no se encuentre un adecuado tejido remanente para realizar una reparación anatómica.

Background: The lesions to the lateral ligaments of the ankle are a common sports related injury. There are multiple surgical technics to address the problem all with a common goal: achieve a proper stability of the ankle. The improvements in the minimal invasive technics as well as those in the materials to fixate bone-tissue have also impacted the technics for lateral stabilization of the ankle. Material and methods: We included all the patients with a diagnosis of lateral ankle instability which underwent surgery with a modify Hemi-Casting procedure with minimal invasive approach during the period between May 2004 and December 2007. We have an average follow-up of 30.3 months. Results: Our patients presented a good outcome with an improvement in the Karlsson's scale of 48.7 points (± 15.6) in the preoperative to 93.6 points (± 9.6) during follow-up. They returned to their sports activities after an average of 5.72 months (± 4.93). We used dynamic X-ray's taken with the Telos system and achieved 81.9% of our patients presented an excellent and good personal satisfaction. Conclusions: The modifications to the Hemi-Castaing procedure to perform it with a minimal invasive technic are reproducible and provide us with another tool for the treatment of this pathology specially in the cases where there is no sufficient tissue to perform an anatomical repair.