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Otodectes cynotis is the agent of otodectic mange, a disease affecting wild and domestic felines, canines and mustelids. It is a highly contagious and pruritic condition and a major cause of otitis externa in dogs. This study was designed to verify the efficacy of NexGard ® PLUS, a combination of afoxolaner, moxidectin and pyrantel pamoate, against natural O. cynotis infestations in dogs. It was a blinded, randomised, single-centre, negative controlled clinical efficacy study. Twenty-four naturally infested dogs were allocated to three groups of eight dogs: an untreated control group, a group treated on Day 0 and a group treated on Days 0 and 29 (both groups were treated per label recommendations). Otoscopic examinations were performed on Days -3, 14, 29, 42 and 55 for clinical otodectic mange evaluation. Ear canal flushings were performed on Day 56 for O. cynotis counts, the primary variable of efficacy, calculated per comparison of live mites in the treated groups, with the untreated control group. The otoscopic examinations revealed treatment effect by Day 14 and a highly significant effect by Day 29, while the conditions remained unchanged or worsened in the untreated control group. The O. cynotis counts revealed reductions of 100% in the group treated once on Day 0 ( p  = 0.0004) and 99.7% ( p  = 0.0006) in the group treated on Days 0 and 29, while 48.8 (geometric mean) live mites were collected in the untreated control group. NexGard ® PLUS was demonstrated to be highly efficacious in dogs naturally infested with O. cynotis following one or two treatments. Otodectes cynotis est l’agent de la gale otodectique, une maladie affectant les félins, les canidés et les mustélidés, sauvages et domestiques. Très contagieuse et prurigineuse, cette affection est une cause majeure d’otite externe chez le chien. Cette étude visait à évaluer l’efficacité de NexGard ® PLUS, une association d’afoxolaner, de moxidectine et de pamoate de pyrantel, contre les infestations naturelles par O. cynotis chez le chien. Il s’agissait d’une étude clinique d’efficacité, monocentrique, randomisée, en double aveugle et contrôlée par un groupe négatif. Vingt-quatre chiens naturellement infestés ont été répartis en trois groupes de huit : un groupe témoin non traité, un groupe traité au jour 0 et un groupe traité aux jours 0 et 29 (les deux derniers groupes ont été traités conformément aux recommandations de l’AMM). Des examens otoscopiques ont été réalisés aux jours -3, 14, 29, 42 et 55 pour l’évaluation clinique de la gale otodectique. Des lavages du conduit auditif ont été effectués au jour 56 pour le dénombrement d’ O. cynotis , principal critère d’efficacité, calculé par comparaison du nombre d’acariens vivants dans les groupes traités avec celui du groupe témoin non traité. Les examens otoscopiques ont révélé un effet du traitement dès le jour 14 et un effet hautement significatif au jour 29, tandis que l’état des chiens du groupe témoin non traité est resté inchangé ou s’est aggravé. Le dénombrement d’ O. cynotis a montré une réduction de 100 % dans le groupe traité une seule fois au jour 0 ( p  = 0,0004) et de 99,7 % ( p  = 0,0006) dans le groupe traité aux jours 0 et 29, tandis que 48,8 acariens vivants (moyenne géométrique) ont été collectés dans le groupe témoin non traité. NexGard ® PLUS s’est avéré très efficace chez les chiens naturellement infestés par O. cynotis après un ou deux traitements.

Chromosome movements and programmed DNA double-strand breaks (DSBs) promote homologue pairing and initiate recombination at meiosis onset. Meiotic progression involves checkpoint-controlled termination of these events when all homologue pairs achieve synapsis and form crossover precursors. Exploiting the temporo-spatial organisation of the C. elegans germline and time-resolved methods of protein removal, we show that surveillance of the synaptonemal complex (SC) controls meiotic progression. In nuclei with fully synapsed homologues and crossover precursors, removing different meiosis-specific cohesin complexes, which are individually required for SC stability, or a SC central region component causes functional redeployment of the chromosome movement and DSB machinery, triggering whole-nucleus reorganisation. This apparent reversal of the meiotic programme requires CHK-2 kinase reactivation via signalling from chromosome axes containing HORMA proteins, but occurs in the absence of transcriptional changes. Our results uncover an unexpected plasticity of the meiotic programme and show how chromosome signalling orchestrates nuclear organisation and meiotic progression. Meiosis-specific cohesins and the synaptonemal complex are essential for meiotic chromosome structure and function. Here the authors show that continued surveillance of these chromosome structures controls meiotic progression by regulating CHK-2, a master regulator of pairing and recombination.

The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in Caenorhabditis elegans . How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin–DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes.

Introduction United States stroke systems are increasingly transitioning from alteplase (TPA) to tenecteplase (TNK). Real-world data on the safety and effectiveness of replacing TPA with TNK before large vessel occlusion (LVO) stroke endovascular treatment (EVT) are lacking. Methods Four Pennsylvania stroke systems transitioned from TPA to TNK during the study period 01/2020–06/2023. LVO stroke patients who received intravenous thrombolysis with TPA or TNK before EVT were reviewed. Multivariate logistic analysis was conducted adjusting for age, sex, National Institute of Health Stroke Scale (NIHSS), occlusion site, last-known-well-to-intravenous thrombolysis time, interhospital-transfer and stroke system. Results Of 635 patients, 309 (48.7%) received TNK and 326 (51.3%) TPA prior to EVT. The site of occlusion was the M1 middle cerebral artery (MCA) (47.7%), M2 MCA (25.4%), internal carotid artery (14.0%), tandem carotid with M1 or M2 MCA (9.8%) and basilar artery (3.1%). A favorable functional outcome (90-day mRS ≤ 2) was observed in 47.6% of TNK and 49.7% of TPA patients ( p  = 0.132). TNK versus TPA groups had similar rates of early recanalization (11.9% vs. 8.4%, p  = 0.259), successful endovascular reperfusion (93.5% vs. 89.3%, p  = 0.627), symptomatic intracranial hemorrhage (3.2% vs. 3.4%, p  = 0.218) and 90-day all-cause mortality (23.1% vs. 21.5%, p  = 0.491). Conclusions This U.S. multicenter real-world clinical experience demonstrated that switching from TPA to TNK before EVT for LVO stroke resulted in similar endovascular reperfusion, safety, and functional outcomes.

Canine sarcoptic mange, caused by Sarcoptes scabiei , is a highly contagious and intensely pruritic skin disease in dogs. It is prevalent worldwide and has zoonotic potential. Therefore, effective treatment is important to safeguard animal welfare and public health. The present clinical field study aimed to confirm the efficacy of NexGard ® Plus, an oral combination of afoxolaner, moxidectin and pyrantel pamoate, in treating dogs naturally infested with S. scabiei . It was a blinded, randomised, single-centre, negative-controlled efficacy study. Twenty naturally infested dogs were allocated into two groups: a group treated on Day 0 and Day 26/28 at the label dose, and an untreated control group. Skin scrapings were conducted similarly, once between Day −6 to 0, then on Days 26/28 and 56 for mite counts. Assessments of clinical signs were conducted at the same time intervals. In the treated group, mite infestations were reduced by 97% after the first treatment and were eliminated (100%) after the second treatment ( p  < 0.0005), while all dogs in the untreated control group remained infested for the whole study. Treated dogs had no pruritus, papules or crusts and clear evidence of hair regrowth by Day 56, unlike the dogs in the control group. This study demonstrated the elimination of S. scabiei mites and significant improvement of sarcoptic mange clinical signs in naturally infested dogs treated with the oral combination of afoxolaner, moxidectin and pyrantel. La gale sarcoptique canine, causée par Sarcoptes scabiei , est une dermatose très contagieuse et extrêmement prurigineuse chez le chien. Elle est répandue dans le monde entier et présente un potentiel zoonotique. Un traitement efficace est donc essentiel pour préserver le bien-être animal et la santé publique. La présente étude clinique de terrain visait à confirmer l’efficacité de NexGard ® Plus, une association orale d’afoxolaner, de moxidectine et de pamoate de pyrantel, dans le traitement des chiens naturellement infestés par S. scabiei . Il s’agissait d’une étude d’efficacité monocentrique, randomisée, en double aveugle et contrôlée par un placebo. Vingt chiens naturellement infestés ont été répartis en deux groupes : un groupe traité aux jours 0 et 26/28 à la dose recommandée, et un groupe témoin non traité. Des prélèvements cutanés ont été effectués de la même manière, une première fois entre le jour −6 et le jour 0, puis aux jours 26, 28 et 56 pour le dénombrement des acariens. L’évaluation des signes cliniques a été réalisée aux mêmes intervalles. Dans le groupe traité, l’infestation par les acariens a diminué de 97% après le premier traitement et a été totalement éliminée (100 %) après le second ( p < 0,0005), tandis que tous les chiens du groupe témoin non traité sont restés infestés pendant toute la durée de l’étude. Les chiens traités ne présentaient ni prurit, ni papules, ni croûtes, et une repousse des poils était clairement visible au jour 56, contrairement aux chiens du groupe témoin. Cette étude a démontré l’élimination des acariens S. scabiei et une amélioration significative des signes cliniques de la gale sarcoptique chez les chiens naturellement infestés traités par l’association orale d’afoxolaner, de moxidectine et de pyrantel.

Nearly 30 % of patients experience complications following cranioplasty after decompressive craniectomy. However, the optimal timing for this procedure is not well established. To compare complication rates for cranioplasty performed at different early monthly intervals after craniectomy. Using the TriNetX Research Network, we included patients who underwent either late cranioplasty (91 days-1 year), or cranioplasty in the first, second, or third month after craniectomy. Propensity score matching was used to match the late cranioplasty group separately with the other three cranioplasty groups based on baseline characteristics in the whole cohort and in a TBI-specific subgroup. Postoperative outcomes were assessed at 6 months after cranioplasty. We analyzed 3241 patients. After matching, 375 patients remained in the first-month, 365 in the second month, and 434 in the third-month group. Compared to late cranioplasty, ICH as a post-operative outcome was significantly more common in the first-month cranioplasty (p = 0.037) and second-month cranioplasty (p = 0.042) groups, while SDH as a post-operative outcome was more frequent in all early cranioplasty groups (p < 0.01). The need for repeat cranioplasty was higher in the first month (p = 0.002) and second month (p = 0.031) groups. Repeat Craniectomy/Craniotomy and CSF leak were more common in the first-month group (p = 0.006 and 0.001, respectively). Mortality was higher in the first month (RR=2.9, 95 %CI:1.5–5.5, p = 0.001) cranioplasty group. Cranioplasty within 2 months after craniectomy was associated with increased postoperative morbidity and mortality, especially for patients without TBI. Prospective studies are needed to establish the best timing for cranioplasty. •Nearly 30 % of patients experience complications following cranioplasty after decompressive craniectomy.•Compare complication rates for cranioplasty performed at different early monthly intervals after craniectomy.•Cranioplasty within 2 months after craniectomy was associated with increased postoperative morbidity and mortality.

Toxoplasma gondii is a zoonotic protozoon with a complex life cycle and the second most important foodborne pathogen in Europe. Surveillance of toxoplasmosis is based on national considerations since there are no mandatory controls along the food chain in the European Union, and underreporting of meat is still a problem in many countries like Greece. The current review provides an overview of T. gondii prevalence, associated risk factors, and surveillance in animals in Greece, focusing on the transmission role of meat and highlighting the control measures that should be adopted by consumers. Sows, wild boars, hares, equines, and cats had lower, while sheep and goats generally had higher seroprevalence than their respective pooled European and global values. Seroprevalence in chickens was similar between Greece and Europe, while there was high variation in cattle studies, with no data regarding dairy products. Though a comprehensive meat safety assurance system is the most effective approach to control the principal biological hazards associated with meat, such as T. gondii, the prerequisite risk categorisation of farms and abattoirs based on EFSA’s proposed harmonised epidemiological indicators has not materialised as yet in Greece. Therefore, comprehensive control strategies are still required to ensure food safety and safeguard public health.

BackgroundMoyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes.ObjectiveIn this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya.MethodsWe conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes.ResultsThe rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563).ConclusionSince both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient’s risk assessment.

Hepatocellular carcinoma (HCC) subtypes differ in terms of histopathology and prognosis. Sarcomatoid HCC is rare and literature concerning the survival of patients with sarcomatoid HCC is scarce. Data of patients with sarcomatoid HCC, diagnosed from 1989 to 2016, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We evaluated the baseline and tumor related data, overall survival (OS), disease-specific survival and the performance (Harrell's concordance index - OS c-index) of the eighth edition of the American Joint Committee on Cancer TNM staging system (AJCC8). In addition, univariate and multivariate forward stepwise cox regression analyses were performed to identify factors associated with increased risk of death. The SEER cohort consisted of 71 patients, mostly males (n=49, 69.0%), of White race (n=51, 71.8%) and the most common stage at presentation was stage IVB (n=30, 42.3%). The overall predictive ability of AJCC8 was mediocre, with an OS c-index=0.577 (SE=0.048). Surgery (hazard ratio=0.25, p<0.001) was significantly associated with reduced risk of death. Advanced TNM stage was not associated with increased risk of death. Sarcomatoid HCC, a rare subtype of HCC, is associated with poor outcomes in terms of overall and disease-specific survival across all disease stages. Surgery seems to be of utmost importance. The eighth edition of the AJCC8 for HCC underperforms in predicting the survival of patients with sarcomatoid subtype.

Brain tumours are a heterogenic group, a subtype of which is arising from glial cells. Pediatric low-grade gliomas are the most common primary CNS tumour group in childhood, representing 25% to over 30% of pediatric CNS tumours. Pediatric high-grade gliomas are relatively rare and have a poor prognosis. Epidemiological studies have reported various potential risk factors, such as demographics, ionizing and nonionizing radiation, allergic conditions, and infections, immunologic, parental, genetic, and developmental risk factors. These risk factors are relatively unclear and understudied; thus, this narrative review aims to summarize all studies connecting risk factors and pediatric gliomas.