A novel neurotropic microsporidium from the swamp guppy Micropoecilia picta from Grenada, West Indies.

A novel microsporidium was observed in wild swamp guppies Micropoecilia picta from Levera Pond within Levera National Park Grenada, West Indies. Initial observations indicated similarity with Pseudoloma neurophilia, an important pathogen in zebrafish Danio rerio. P. neurophilia exhibit broad host specifity, including members of the family Poecillidae, and both parasites infect the central nervous system. However, spore morphology and molecular phylogeny based on rDNA showed that the swamp guppy microsporidium (SGM) is distinct from P. neurophilia and related microsporidia (Microsporidium cerebralis and M. luceopercae). Spores of the SGM were smaller than others in the clade (3.6 µm long). Differences were also noted in histology; the SGM formed large aggregates of spores within neural tissues along with a high incidence of numerous smaller aggregates and single spores within the surface tissue along the ventricular spaces that extended submeninx, whereas P. neurophilia and M. cerebralis infect deep into the neuropile and cause associated lesions. Analysis of small subunit ribosomal DNA sequences showed that the SGM was <93% similar to these related microsporidia. Nevertheless, one of 2 commonly used PCR tests for P. neurophilia cross reacted with tissues infected with SGM. These data suggest that there could be other related microsporidia capable of infecting zebrafish and other laboratory fishes that are not being detected by these highly specific assays. Consequently, exclusive use of these PCR tests may not accurately diagnose other related microsporidia infecting animals in laboratory and ornamental fish facilities.

Speed of clinical improvement in the real-world setting from patient-reported Psoriasis Symptoms and Signs Diary: Secondary outcomes from the Psoriasis Study of Health Outcomes through 12 weeks.

BACKGROUND: Rapid skin improvement is a key treatment goal of patients with moderate-to-severe psoriasis (PsO). OBJECTIVES: To compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study that compares the effectiveness of anti-interleukin (IL)-17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7-day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0-10). Symptom and sign summary scores (0-100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM). RESULTS: Across cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti-IL-17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality-of-life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12. CONCLUSIONS: Treatment with anti-IL-17A biologics, particularly ixekizumab, resulted in rapid and sustained patient-reported improvements in psoriasis symptoms and signs compared with other biologics in a real-world setting.

Screening of biological activities of fungi associated with pistachio bark beetle, Chaetoptelius vestitus (Coleoptera, Curculionidae), infesting pistachio cultivations in Tunisia.

AIMS: In this study, we aimed to explore the enzymatic diversity, the entomopathogenic and the antimicrobial potentialities of fungi associated with the pistachio bark beetle, Chaetoptelius vestitus. METHODS AND RESULTS: A total of 40 isolates were screened for enzymatic diversity. Most of them, 92·5%, were able to produce at least two of the screened enzymes. Pathogenic assays performed on C. vestitus showed a high entomopathogenic activity of the isolates Ata_io_1 (A. tamarii), Fve_io_1 (F. verticillioides), Tpi_io_1 (T. pinophilus), Pal_io_1 (P. album), Pbi_io_2 (Penicillium bilaiae) and Pch_io_1 (P. chrysogenum), as based on mean mortality of C. vestitus. A screening of antimicrobial activity using well diffusion method showed that the isolates Tro_io_1 (T. pinophilus), Tat_io_1 (T. atroroseus) and Pch_io_1 (P. chrysogenum) presented the highest antibacterial activity. Furthermore, Mgu_io_1 (M. guilliermondii), Asc_io_1 (A. sclerotiorum), Ata_io_1 (A. tamarii), G. lavendula (Gla_io_1), Pva_io_1 (P. variotii), Pul_io_1 (P. ulaiense), Tat_io_1 (T. atroroseus) and Tro_io_1 (T. roseum) were active against at least two of the three tested fungal phytopathogens. CONCLUSIONS: Fungal isolates representing entomopathogenic activity and a broad spectrum of antimicrobial activities can be considered as promising resources for biological pistachio trees protection. SIGNIFICANCE AND IMPACT OF THE STUDY: Fungi associated with C. vestitus were investigated for detecting their potential biotechnological applications.

Phytopathogenic and antagonistic potentialities of fungi associated with pistachio bark beetle, Chaetoptelius vestitus (Coleoptera, Curculionidae), infesting pistachio (Pistacia vera) in Tunisia.

AIM: This study investigated the biodiversity of fungi associated with the pistachio bark beetle, Chaetoptelius vestitus, in Tunisia. We evaluated the phytopathogenic activities and tested antagonistic potentialities with respect to phytopathogens. METHODS AND RESULTS: A total of 41 fungal isolates were randomly isolated from C. vestitus adults and galleries. We identified 28 species belonging to 13 genera using ITS sequences of the ribosomal RNA operons. Pathogenicity assays performed using the excised shoot method revealed that isolates Aal_io_1 (Alternaria alternata), Feq_io_1 (Fusarium equiseti), Fgra_io_1 (Fusarium graminearum), Fve_io_1 (Fusarium verticilloides), Tro_io_1 (Trichothecium roseum) and Nqu_io_1 (Nothophoma quercina) displayed a high pathogenic activity on pistachio stems. Estimation of the antagonistic potentialities of isolated fungi against several phytopathogenic isolates as tested using a dual-culture method showed that isolates Tpi_io_1 (Talaromyces pinophilus), Pbi_io_2 (Penicillium bilaiae), Asc_io_1 (Aspergillus sclerotiorum) and Gla_io_1 (Geosmithia lavendula) displayed a broad range of antagonistic activities. CONCLUSION: Fungi associated with C. vestitus had a variable range of pathogenic activity on pistachio stem. Phytopathogenic fungi were antagonized by different fungal isolates which could be promising in pistachio protection against phytopathogenic fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first that investigated the diversity of fungi associated with C. vestitus and evaluated both their phytopathogenic activity and antagonistic potential against fungal phytopathogens.

[Peripheral arterial occlusive disease as predictor of high atherosclerotic burden]. / Periphere arterielle Verschlusskrankheit als Prädiktor einer hohen Atheroskleroselast.

Atherosclerosis is a disease which affects the whole arterial vascular tree. In particular patients with peripheral arterial occlusive disease (PAOD) often suffer from additional atherosclerotic manifestations in other vascular territories. This has a direct impact on cardiovascular prognosis. Atherosclerosis is an inflammatory disease. A high inflammatory burden is associated with polyvascular atherosclerosis and also with the occurrence of cardiovascular events. Control of cardiovascular risk factors is crucial for the treatment of patients with polyvascular atherosclerosis. In addition, anticoagulation treatment is very important in patients with atherosclerosis. Moreover, exercise training is an important treatment option in PAOD patients not only to improve walking distance but also for multiple additional positive effects. So far the role of anti-inflammatory treatment is not clear and must be further elaborated by future clinical research.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

The segmental diffusivity profile of amyotrophic lateral sclerosis associated white matter degeneration.

BACKGROUND AND PURPOSE: Magnetic resonance diffusivity indices have been repeatedly proposed as biomarkers of neurodegeneration in amyotrophic lateral sclerosis (ALS), but no consensus exists as to which diffusivity parameter is the most sensitive to identify early degenerative changes. Despite numerous studies, surprisingly little is known of the segmental vulnerability of the corticospinal tracts and corpus callosum. Our objective was to characterize the core three-dimensional white matter signature of ALS, to describe phenotype-specific patterns of white matter degeneration and to evaluate the diffusivity profile of individual patients and controls in specific white matter segments. METHODS: A large neuroimaging study was undertaken with 62 patients and 55 age-matched healthy controls. White matter alterations were explored based on fractional anisotropy and radial, mean and axial diffusivity indices. Atlas-based region of interest analyses were carried out in the corona radiata, internal capsules, cerebral peduncles, and in the splenium, body and genu of the corpus callosum. Percentage change and receiver operating characteristic (ROC) curves were used to characterize disease-state discriminating diffusivity measures and white matter regions. RESULTS: Bulbar onset patients exhibit extensive corticobulbar tract involvement in the genu of the internal capsule and in the lateral fibres of the corona radiata subjacent to the bulbar representation of the motor homunculus. Spinal onset patients show predominantly posterior internal capsule involvement and medial corona radiata pathology. ROC curve analyses revealed that diffusivity measures of the cerebral crura best discriminate patients and controls (area under the curve 80.1%). CONCLUSIONS: Amyotrophic lateral sclerosis is associated with a core, disease-specific three-dimensional white matter signature which is best demonstrated by radial diffusivity measurements. The main ALS motor phenotypes are manifestations of the relatively selective involvement of corticospinal and corticobulbar fibres.

Diagnostic approach in lymphoplasmacytic plaque.

BACKGROUND: Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. OBJECTIVE: To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. METHODS: We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. RESULTS: We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. CONCLUSIONS: LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

Comparative Effectiveness and Durability of Biologics in Clinical Practice: Month 12 Outcomes from the International, Observational Psoriasis Study of Health Outcomes (PSoHO).

INTRODUCTION: Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12 months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different measures of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness. RESULTS: Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month 12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month 12, with no significant differences between the cohorts in the adjusted analyses. At month 12, the response rates across the individual biologics were 53.5-72.6% for the primary outcome, 27.6-48.3% for PASI100, and 41.7-61.4% for PASI90. CONCLUSIONS: These results show the comparative effectiveness of biologics at 6 and 12 months in the real-world setting.

Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas.

INTRODUCTION: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement. MATERIALS AND METHODS: We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1. RESULTS: We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1). CONCLUSIONS: The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial. PATIENT SUMMARY: In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.

Asymmetric activity of NetrinB controls laterality of the Drosophila brain.

Left-Right (LR) asymmetry of the nervous system is widespread across animals and is thought to be important for cognition and behaviour. But in contrast to visceral organ asymmetry, the genetic basis and function of brain laterality remain only poorly characterized. In this study, we performed RNAi screening to identify genes controlling brain asymmetry in Drosophila. We found that the conserved NetrinB (NetB) pathway is required for a small group of bilateral neurons to project asymmetrically into a pair of neuropils (Asymmetrical Bodies, AB) in the central brain in both sexes. While neurons project unilaterally into the right AB in wild-type flies, netB mutants show a bilateral projection phenotype and hence lose asymmetry. Developmental time course analysis reveals an initially bilateral connectivity, eventually resolving into a right asymmetrical circuit during metamorphosis, with the NetB pathway being required just prior symmetry breaking. We show using unilateral clonal analysis that netB activity is required specifically on the right side for neurons to innervate the right AB. We finally show that loss of NetB pathway activity leads to specific alteration of long-term memory, providing a functional link between asymmetrical circuitry determined by NetB and animal cognitive functions.

Multilocus sequence analysis (MLSA) of 'Rickettsiella costelytrae' and 'Rickettsiella pyronotae', intracellular bacterial entomopathogens from New Zealand.

AIMS: Larvae of scarab beetles live in the soil and are frequently hosts for microbial pathogens. In New Zealand, larvae of the grass grub, Costelytrae zealandica (Coleoptera: Scarabaeidae), and manuka beetles, Pyronota spp. (Coleoptera: Scarabaeidae), have been collected from field populations showing loss of vigour and a whitened appearance. Diagnosis indicated an intracellular infection of fat body tissues by Rickettsiella-like micro-organisms. Rickettsiella bacteria are under evaluation as a possible new source of insect bio-control agents for important agricultural pests as, e.g. scarabaeid and elaterid larvae. The present study aimed at the unequivocal molecular taxonomic identification and comparison of the bacteria associated with Costelytra and Pyronota. METHODS AND RESULTS: Electron microscopy and phylogenetic reconstruction using a multilocus sequence analysis approach based on the 16S ribosomal RNA gene together with four protein-encoding markers (ftsY, gidA, rpsA, and sucB) demonstrated that both bacteria from New Zealand are phylogenetically closely related, but not identical, and belong to the taxonomic genus Rickettsiella. CONCLUSIONS: The bacteria under study should be referred to as pathotypes 'Rickettsiella costelytrae' and 'Rickettsiella pyronotae', respectively. Moreover, on the basis of the currently accepted systematic organization of the genus Rickettsiella, both pathotypes should be considered synonyms of the nomenclatural type species, Rickettsiella popilliae. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates that Rickettsiella bacteria are geographically widespread pathogens of scarabaeid larvae. Implications of the phylogenetic findings presented for the stability of host adaptation by Rickettsiella bacteria are critically discussed.

High energy transmission of Al2O3 doped with light transition metals.

The transmission of transparent colored ceramics based on Al(2)O(3) doped with light transition metals is measured in the visible and infrared range. To clarify the role of the dopands we perform ab initio calculations. We discuss the electronic structure and present optical spectra obtained in the independent particle approximation. We argue that the gross spectral features of Co- and Ni-doped Al(2)O(3) samples are described by our model, while the validity of the approach is limited for Cr-doped Al(2)O(3).

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures.