Two Cases of Orbital Myositis as a Rare Feature of Lyme Borreliosis

Myositis has been reported as a rare manifestation of Lyme disease, and the Lyme disease spirochetes can be an important consideration in the differential diagnosis of unusual cases of myositis, especially in patients who live in or travel to endemic areas. We report the case of two patients who presented with focal orbital myositis which are rare localization for Lyme disease. Myositis were confirmed by magnetic resonance imaging. Diagnosis criteria for Borrelia burgdorferi (B. burgdorferi) infection was supported by (i) medical history (tick bite in an endemic area), (ii) systemic clinical findings (Erythema migrans, neurological manifestation or arthritis), (iii) positive Lyme serology and/or the detection of B. burgdorferi DNA by polymerase chain reaction, as well as (iv) exclusion of other infectious and inflammatory causes. The current cases are reviewed in the context of findings from previous myositis descriptions

Panton–Valentine Leukocidin Colocalizes with Retinal Ganglion and Amacrine Cells and Activates Glial Reactions and Microglial Apoptosis

International audienceExperimental models have established Panton-Valentine leukocidin (PVL) as a potential critical virulence factor during Staphylococcus aureus endophthalmitis. In the present study, we aimed to identify retinal cell targets for PVL and to analyze early retinal changes during infection. After the intravitreous injection of PVL, adult rabbits were euthanized at different time points (30 min, 1, 2, 4 and 8 h). PVL location in the retina, expression of its binding receptor C5a receptor (C5aR), and changes in Müller and microglial cells were analyzed using immunohistochemistry, Western blotting and RT-qPCR. In this model of PVL eye intoxication, only retinal ganglion cells (RGCs) expressed C5aR, and PVL was identified on the surface of two kinds of retinal neural cells. PVL-linked fluorescence increased in RGCs over time, reaching 98% of all RGCs 2 h after PVL injection. However, displaced amacrine cells (DACs) transiently colocalized with PVL. Müller and microglial cells were increasingly activated after injection over time. IL-6 expression in retina increased and some microglial cells underwent apoptosis 4 h and 8 h after PVL infection, probably because of abnormal nitrotyrosine production in the retina

TRUSTED: The Paired 3D Transabdominal Ultrasound and CT Human Data for Kidney Segmentation and Registration Research

Inter-modal image registration (IMIR) and image segmentation with abdominal Ultrasound (US) data has many important clinical applications, including image-guided surgery, automatic organ measurement and robotic navigation. However, research is severely limited by the lack of public datasets. We propose TRUSTED (the Tridimensional Renal Ultra Sound TomodEnsitometrie Dataset), comprising paired transabdominal 3DUS and CT kidney images from 48 human patients (96 kidneys), including segmentation, and anatomical landmark annotations by two experienced radiographers. Inter-rater segmentation agreement was over 94 (Dice score), and gold-standard segmentations were generated using the STAPLE algorithm. Seven anatomical landmarks were annotated, important for IMIR systems development and evaluation. To validate the dataset's utility, 5 competitive Deep Learning models for automatic kidney segmentation were benchmarked, yielding average DICE scores from 83.2% to 89.1% for CT, and 61.9% to 79.4% for US images. Three IMIR methods were benchmarked, and Coherent Point Drift performed best with an average Target Registration Error of 4.53mm. The TRUSTED dataset may be used freely researchers to develop and validate new segmentation and IMIR methods.Comment: Alexandre Hostettler, and Toby Collins share last authorshi

Cytokine Profiles in Toxoplasmic and Viral Uveitis

BackgroundUveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context MethodsUsing a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract ResultsFive mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-γ, IL-6, and macrophage inflammatory protein-1β were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis ConclusionsWe found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatmen

PLoS Biol

The eukaryotic XPD helicase is an essential subunit of TFIIH involved in both transcription and nucleotide excision repair (NER). Mutations in human XPD are associated with several inherited diseases such as xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. We performed a comparative analysis of XPD from Homo sapiens and Chaetomium thermophilum (a closely related thermostable fungal orthologue) to decipher the different molecular prerequisites necessary for either transcription or DNA repair. In vitro and in vivo assays demonstrate that mutations in the 4Fe4S cluster domain of XPD abrogate the NER function of TFIIH and do not affect its transcriptional activity. We show that the p44-dependent activation of XPD is promoted by the stimulation of its ATPase activity. Furthermore, we clearly demonstrate that XPD requires DNA binding, ATPase, and helicase activity to function in NER. In contrast, these enzymatic properties are dispensable for transcription initiation. XPD helicase is thus exclusively devoted to NER and merely acts as a structural scaffold to maintain TFIIH integrity during transcription

Evaluation of branched GDGTs and leaf wax n-alkane δ2H as (paleo) environmental proxies in East Africa

The role of mountain evolution on local climate is poorly understood and potentially underestimated in climate models. One prominent example is East Africa, which underwent major geodynamic changes with the onset of the East African Rift System (EARS) more than 250 Myr ago. This study explores, at the regional East African scale, a molecular approach for terrestrially-based paleo-climatic reconstructions that takes into account both changes in temperature and in altitude, potentially leading to an improved concept in paleo-climatic reconstructions. Using surface soils collected along pronounced altitudinal gradients in Mt. Rungwe (n=40; Southwest Tanzania) and Mt. Kenya (n=20; Central Kenya), we investigate the combination of 2 terrestrial proxies, leaf wax n-alkane δ2H (δ2Hwax) and branched glycerol dialkyl glycerol tetraether (br GDGT) membrane lipids, as (paleo) elevation and (paleo) temperature proxies, respectively. At the mountain scale, a weak link between δ2Hwax and altitude (R2 = 0.33) is observed at Mt. Kenya, but no relationship is observed at Mt. Rungwe. It is likely that additional parameters, such as decreasing relative humidity (RH) or vegetation changes with altitude, are outcompeting the expected 2H-depletion trend along Mt. Rungwe. In contrast, br GDGT-derived absolute mean annual air temperature (MAAT) and temperature lapse rate (0.65 °C/100 m) for both mountains are in good agreement with direct field measurements, further supporting the robustness of this molecular proxy for (paleo) temperature reconstructions. At the regional scale, estimated and observed δ2H data in precipitation along 3 mountains in East Africa (Mts. Rungwe, Kenya and Kilimanjaro) highlight a strong spatial heterogeneity, preventing the establishment of a regional based calibration of δ2Hwax for paeloaltitudinal reconstructions. Different from that, an improved regional soil calibration is developed between br GDGT distribution and MAAT by combining the data from this study (Mts. Rungwe and Kenya) with previous results from East African surface soils along Mts. Kilimanjaro (Tanzania) and Rwenzori (Uganda). This new regional calibration, based on 105 samples, improves both the R2 (0.77) and RMSE (root mean square error; 2.4 °C) of br GDGT-derived MAAT over the global soil calibrations previously established (R2 = 0.56; RMSE = 4.2 °C) and leads to more accurate (paleo) temperature reconstructions in the region

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International audienceBackground: Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.Methods: We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced.Results: Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients.Conclusion: This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit