Chronic granulomatous disease: the European experience.

CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst", essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (approximately 1:250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91(phox) deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (<1%) were found only sporadically. Lesions induced by inoculation with BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with gamma-interferon. 24 patients (6%) had received a stem cell transplantation. The most prominent reason of death was pneumonia and pulmonary abscess (18/84 cases), septicemia (16/84) and brain abscess (4/84). These data provide further insight in the clinical course of CGD in Europe and hopefully can help to increase awareness and optimize the treatment of these patients

Outcome of children with panarteritis nodosa: a series of 30 cases

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Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

OBJECTIVE: To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. RESULTS: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. CONCLUSIONS: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings

Seasonal Trends in Acoustic Detection of Marine Mammals in Baffin Bay and Melville Bay, Northwest Greenland

The expansion of hydrocarbon exploration in northwest Greenland has made it increasingly important to understand the occurrence of marine mammals in the region. We describe the seasonal occurrence of marine mammals and the spatial distribution of their calls in Baffin Bay and Melville Bay. Four Autonomous Multichannel Acoustic Recorders (AMARs) were deployed during summer 2012 (late July to early October), five recorders during September 2013, and two recorders from late September 2013 to early September 2014. The call presence of several species was analyzed using automatic call detection and manual verification analysis methods. A novel approach to discern narwhal (Monodon monoceros) clicks from beluga (Delphinapterus leucas) clicks was implemented during the verification process. Narwhal calls were detected in spring and fall, showing a south-to-north migration pattern in spring and a north-to-south migration pattern in fall. Few beluga whales were detected during fall 2013 and spring 2014. Bearded seal (Erignathus barbatus) calls were detected mainly during spring (mating period). A small number of bowhead whale calls (Balaena mysticetus) were detected during fall 2013 and spring and summer 2014. For the first time at this latitude in Baffin Bay, long-finned pilot whales (Globicephala melas) and sperm whales (Physeter macrocephalus) were detected during summer and fall. Our results suggest that the presence of marine mammals in Baffin Bay and Melville Bay is governed mainly by the annual cycle of sea ice formation and decay

Gray Whale (Eschrictius robustus) Call Types Recorded During Migration off the West Coast of Vancouver Island

Gray whale (Eschrichtius robustus) vocalizing behavior varies over its range, both in call type and frequency. This study adds to the growing body of passive acoustic research outside of the calving/breeding lagoons, and moves toward a description of calling behaviors throughout the whales' range. Data are presented here from acoustic surveys for two northward and one southward migration, with recordings taken off the west coast of Vancouver Island. We found gray whales to be highly sonorous, with extensive calling during the study periods of February to May for northward migrations and September to the end of January for southward travel. Low frequency moans were the most prevalent call type, with others, including knocks, up- and down sweeps, and rumbles, recorded in varying numbers. We hypothesize that calling is an aid for navigation and orientation of the herd along the migration route, in addition to holding more social functions usually assigned to baleen whale calling

Junctophilin-2 tethers T-tubules and recruits functional L-type calcium channels to lipid rafts in adult cardiomyocytes

Aim: In cardiomyocytes, transverse tubules (T-tubules) associate with the sarcoplasmic reticulum (SR), forming junctional membrane complexes (JMCs) where L-type calcium channels (LTCCs) are juxtaposed to Ryanodine receptors (RyR). Junctophilin-2 (JPH2) supports the assembly of JMCs by tethering T-tubules to the SR membrane. T-tubule remodeling in cardiac diseases is associated with down-regulation of JPH2 expression suggesting that JPH2 plays a crucial role in T-tubule stability. Furthermore, increasing evidence indicate that JPH2 might additionally act as a modulator of calcium signaling by directly regulating RyR and LTCCs. This study aimed at determining whether JPH2 overexpression restores normal T-tubule structure and LTCC function in cultured cardiomyocytes. Methods and results: Rat ventricular myocytes kept in culture for 4 days showed extensive T-tubule remodeling with impaired JPH2 localization and relocation of the scaffolding protein Caveolin3 (Cav3) from the T-tubules to the outer membrane. Overexpression of JPH2 restored T-tubule structure and Cav3 relocation. Depletion of membrane cholesterol by chronic treatment with Methyl-β-cyclodextrin (MβCD) countered the stabilizing effect of JPH2 overexpression on T-tubules and Cav3. Super-resolution scanning patch-clamp showed that JPH2 overexpression greatly increased the number of functional LTCCs at the plasma membrane. Treatment with MβCD reduced LTCC open probability and activity. Proximity ligation assays showed that MβCD did not affect JPH2 interaction with RyR and the pore-forming LTCC subunit Cav1.2, but strongly impaired JPH2 association with Cav3 and the accessory LTCC subunit Cavβ2. Conclusions: JPH2 promotes T-tubule structural stability and recruits functional LTCCs to the membrane, most likely by directly binding to the channel. Cholesterol is involved in the binding of JPH2 to T-tubules as well as in the modulation of LTCC activity. We propose a model where cholesterol and Cav3 support the assembly of lipid rafts which provide an anchor for JPH2 to form JMCs and a platform for signaling complexes to regulate LTCC activity

Beluga Vocalizations Decrease in Response to Vessel Traffic in the Mackenzie River Estuary

Vessel traffic negatively affects marine mammals by causing behavioural disturbance, acoustic masking, contamination (i.e., oil spills), and ship strikes. Few studies have examined the effects of vessels on marine mammals in the Arctic, but beluga whales appear to be especially sensitive to vessel traffic. We examine how the vocalizations of belugas are impacted by vessel traffic in the Tarium Niryutait Marine Protected Area in the Mackenzie River estuary of the western Canadian Arctic. Between one and four acoustic recorders were deployed between June and August each year between 2015 and 2018 near the only shipping channel at this site. We examined beluga vocalizations from acoustic recordings over four summers and assessed how the distance to the nearest vessel passing the acoustic recorder affected the number of vocalizations. Beluga vocalizations within the range of the acoustic recorder decreased significantly when vessels were within 5 km of the acoustic recorder. This result suggests either that belugas are avoiding the vessel or that they reduce their vocalization in response to vessel traffic. Future work is needed to assess exactly how belugas are reacting to vessel traffic in this area and what the long-term consequences of these reactions are. Management measures for reducing these impacts must be carefully considered, especially since these vessels are very restricted in where they can travel, and many of the vessels are necessary for the livelihoods of local communities.La circulation maritime a des effets négatifs sur les mammifères marins, car elle entraîne des perturbations comportementales, masque leurs signaux acoustiques et engendre de la contamination (comme des déversements de pétrole) et des collisions. Bien que peu d’études aient examiné les effets des bateaux sur les mammifères marins de l’Arctique, les bélugas semblent particulièrement sensibles à la circulation maritime. Dans cet article, nous examinons en quoi les vocalisations des bélugas sont touchées par la circulation maritime dans la zone de protection marine de Tarium Niryutait faisant partie de l’estuaire du fleuve Mackenzie, dans l’ouest de l’Arctique canadien. Entre un et quatre enregistreurs acoustiques ont été déployés de juin à août de chaque année entre 2015 et 2018, à proximité du seul chenal de navigation de l’endroit. Nous avons examiné les vocalisations des bélugas prélevées à l’aide des enregistreurs acoustiques au cours de quatre étés, et évalué en quoi la distance du bateau passant le plus près de l’enregistreur acoustique avait un effet sur le nombre de vocalisations. Les vocalisations des bélugas dans la zone de l’enregistreur acoustique diminuaient considérablement lorsque les bateaux se trouvaient à moins de cinq kilomètres de l’enregistreur. Ce résultat suggère soit que les bélugas évitent les bateaux, soit qu’ils réduisent leurs vocalisations en réponse à la circulation maritime. Il y a lieu de pousser cette étude plus loin pour évaluer exactement comment les bélugas réagissent à la circulation des bateaux dans cette région, et quelles sont les conséquences à long terme de ces réactions. Il y a lieu aussi de considérer avec soin des mesures de gestion pour réduire ces incidences, surtout parce que les déplacements de ces bateaux sont assujettis à de nombreuses restrictions et parce que grand nombre des bateaux qui passent par là sont nécessaires à la subsistance des collectivités de la région. &nbsp

Using acoustic monitoring to reveal nearly year-round presence of humpback whales (Megaptera novaeangliae) in the waters of southern Iceland

Publisher Copyright: © 2024 The Author(s). Marine Mammal Science published by Wiley Periodicals LLC on behalf of Society for Marine Mammalogy.Icelandic waters are a crucial feeding ground for North Atlantic humpback whales, yet their occurrence in these subarctic waters remains underexplored. This study examined seasonal and diel patterns in humpback whale occurrence off the Vestmannaeyjar archipelago, southern Iceland, from June 2018 to May 2019, using automated acoustic detections from bottom-moored hydrophones. Vocalizations were manually categorized into social calls, song fragments, or songs. Further classification identified seven social sound types and 25 unique song units. Humpback whales were detected on 126 out of 329 recording days and were present in nearly all months except April and May. Social calls were most common in summer and fall, while song fragments and songs were prevalent in winter. No diel singing pattern was observed. These findings suggest southern Iceland serves as a vital habitat for humpback whales, acting as a feeding ground in summer and a migration stopover or overwintering site in winter. The study underscores the potential of acoustic monitoring to uncover important habitats year-round, especially when field observations are scarce, and emphasizes the need for ongoing monitoring of habitat use. Continued acoustic monitoring could provide further insights into the whales' behavioral patterns and preferences, essential for their conservation.Peer reviewe