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Abstract In this study, we analyze the effects of technology availability, political coordination, and behavioral change on transformation pathways toward net-zero greenhouse gas emissions in the European Union by 2050. We implemented an iterative stakeholder dialogue to co-design the scenarios that were calculated using a global multi-regional energy-economy-land-climate model. We find that in scenarios without behavioral change and with restriction of technologies, the target of greenhouse gas neutrality in the European Union cannot be reached. Already a target of 200 Mt CO2eq/yr requires CO2 prices above 100 €/tCO2 in 2030 across all sectors in all scenarios. The required CO2 price can increase to up to 450 €/tCO2 by 2030 if technologies are constrained, if no complementary regulatory measures are implemented, and if changes in consumer behavior towards a more sustainable lifestyle do not materialize.

IntroductionStatistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective.MethodsPreliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification.ResultsAs expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset.DiscussionThis study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses.

Abstract Predicting and monitoring battery life early and across chemistries is a significant challenge due to the plethora of degradation paths, form factors, and electrochemical testing protocols. Existing models typically translate poorly across different electrode, electrolyte, and additive materials, mostly require a fixed number of cycles, and are limited to a single discharge protocol. Here, an attention-based recurrent algorithm for neural analysis (ARCANA) architecture is developed and trained on an ultra-large, proprietary dataset from BASF and a large Li-ion dataset gathered from literature across the globe. ARCANA generalizes well across this diverse set of chemistries, electrolyte formulations, battery designs, and cycling protocols and thus allows for an extraction of data-driven knowledge of the degradation mechanisms. The model’s adaptability is further demonstrated through fine-tuning on Na-ion batteries. ARCANA advances the frontier of large-scale time series models in analytical chemistry beyond textual data and holds the potential to significantly accelerate discovery-oriented battery research endeavors.

Through a collaborative effort across six Sub-Saharan African countries, using recognized international assessment techniques, 23 stocks of three tick species (Rhipicephalus microplus, Rhipicephalus appendiculatus and Amblyomma variegatum) of economic importance for rural small holder farming communities from East and West Africa were collected from cattle, and evaluated in in vitro larval packet tests (LPT). The results demonstrated medium to high resistance to chlorfenvinphos and amitraz across species. Rhipicephalus microplus demonstrated high level alpha-cypermethrin and cypermethrin resistance. Stocks of A. variegatum (West Africa) and R. appendiculatus (Uganda) demonstrated medium level ivermectin resistance.The four least susceptible stocks (East and West African R. microplus, A. variegatum and R. appendiculatus) were taken into in vivo controlled cattle studies where fipronil was found effective against West and East African R. microplus isolates although persistent efficacy failed to reach 90%. Cymiazole and cypermethrin, and ivermectin based acaricides were partially effective against R. microplus without persistent efficacy. Flumethrin spray-on killed A. variegatum within 72 h for up to 10 days posttreatment, however product application was directly to tick attachment sites, which may be impractical under field conditions. A flumethrin pour-on formulation on goats provided persistent efficacy against A. variegatum for up to one-month. Therapeutic control was achieved against R. appendiculatus through weekly spraying cattle with flumethrin, amitraz or combined cymiazole and cypermethrin. A fipronil pour-on product offered four-week residual control against R. appendiculatus (with slow onset of action).Few studies have assessed and directly compared acaricidal activity in vitro and in vivo. There was some discordance between efficacy indicated by LPT and in vivo results. This observation calls for more research into accurate and affordable assessment methods for acaricide resistance.No single active or product was effective against all three tick species, emphasising the need for the development of alternative integrated tick management solutions.

Objective Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiac disorder caused by deposition of wild type or mutated transthyretin. As ATTR-CM is associated with conduction disease, we sought to determine its prevalence in patients with idiopathic high-degree atrioventricular (AV) block requiring permanent pacemaker (PPM) implantation.Methods Consecutive patients aged 70–85 years undergoing PPM implantation for idiopathic high-degree AV block between November 2019 and November 2021 were offered a 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan. Demographics, comorbidities, electrocardiographic and imaging data from the time of device implantation were retrospectively collected.Results 39 patients (79.5% male, mean (SD) age at device implantation 76.2 (2.9) years) had a DPD scan. 3/39 (7.7%, all male) had a result consistent with ATTR-CM (Perugini grade 2 or 3). Mean (SD) maximum wall thickness of those with a positive DPD scan was 19.0 mm (3.6 mm) vs 11.4 mm (2.7 mm) in those with a negative scan (p=0.06). All patients diagnosed with ATTR-CM had spinal canal stenosis and two had carpal tunnel syndrome.Conclusions ATTR-CM should be considered in older patients requiring permanent pacing for high-degree AV block, particularly in the presence of left ventricular hypertrophy, carpal tunnel syndrome or spinal canal stenosis.

Intraplacental choriocarcinoma (IC), or choriocarcinoma in situ, is a rare disease on the gestational trophoblastic disease (GTD) spectrum, with

Abstract Background Orally administered fluralaner (13.64% w/w) is effective for treating canine generalized demodicosis. A study was initiated to assess the efficacy of a novel 5.46% w/w fluralaner chewable tablet formulation for monthly administration in the treatment of this disease. Methods Client-owned dogs diagnosed with generalized demodicosis were acclimatized to laboratory conditions and randomized to receive either orally administered fluralaner (Bravecto® 1-Month) (10.0 to 14.4 mg/kg body weight) (n = 8) or topical imidacloprid-moxidectin (Advocate® for dogs, Elanco) applied per label on days 0, 28, and 56 (n = 8), or more frequently for ongoing severe demodicosis. On days −2, 28, 56, and 84, deep skin scrapings were taken from five sites on each dog for mite identification and counting, and semiquantitative clinical assessments of generalized demodicosis were recorded. Primary efficacy was based upon arithmetic mean mite count reductions relative to pre-treatment. Results By day 28, mean pre-treatment mite counts, > 600 in both groups, were significantly reduced by 99.7% and 89.5% (both P 90% hair regrowth on day 84. Conclusion Three consecutive monthly orally administered treatments with fluralaner (5.46% w/w) flavored chewable tablets (minimum dose rate 10 mg/kg body weight) eliminated Demodex canis mites from dogs diagnosed with generalized demodicosis. Graphical Abstract

Abstract Background Haemaphysalis longicornis ticks are reported on dogs from an increasing geographic range. This study aimed to determine the sustained efficacy of Seresto® collars (imidacloprid/flumethrin) against experimental infestations of H. longicornis in dogs. Methods Twenty-four Beagle dogs previously assessed for their suitability to harbor ticks were included in the study and randomized into three groups of eight dogs each. Two of the groups were treated with collars at different time points: at the first tick infestation, dogs in group 1 had already worn collars for 92 days, while dogs in group 2 had received collars only on the previous day, thus allowing evaluation of two different treatment durations at the same point in time. Infestation of the treated groups was conducted at 1, 7, 28, and 56 days (group 2) and 92, 119, 147, 168, 196, 227, and 238 days (group 1) after collar placement. Group 3 served as untreated control and was infested whenever the dogs of the other two groups were infested. Infestations were conducted using 50 viable, adult, unfed female ticks of a US isolate of H. longicornis per dog. Ticks were removed and counted 48 h after each infestation. Health and body weight of the dogs were monitored throughout the study. The efficacy against ticks was calculated for groups 1 and 2 based on arithmetic mean values at each assessment day according to Abbott’s formula. The mean post-treatment H. longicornis tick counts were compared statistically between treatments, using an analysis of variance with a treatment effect untransformed tick count. Results Dogs in the control group were adequately infested at all tick counts. Efficacy was 88.2% on day 3, however well above 90% (i.e., 98.3 to 100%) at all other time points up to day 240. Statistical analysis confirmed significantly different live tick counts (P

Abstract Background Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus. Methods Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs. Results Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P

Several artificial intelligence-based models have been presented for the detection of periodontal bone loss (PBL), mostly using convolutional neural networks, which are the state of the art in deep learning. Given the emerging breakthrough of transformer networks in computer vision, we aimed to evaluate various models for automatized PBL detection. An image data set of 21,819 anonymized periapical radiographs from the upper/lower and anterior/posterior regions was assessed by calibrated dentists according to PBL. Five vision transformer networks (ViT-base/ViT-large from Google, BEiT-base/BEiT-large from Microsoft, DeiT-base from Facebook/Meta) were utilized and evaluated. Accuracy (ACC), sensitivity (SE), specificity (SP), positive/negative predictive value (PPV/NPV) and area under the ROC curve (AUC) were statistically determined. The overall diagnostic ACC and AUC values ranged from 83.4 to 85.2% and 0.899 to 0.918 for all evaluated transformer networks, respectively. Differences in diagnostic performance were evident for lower (ACC 94.1–96.7%; AUC 0.944–0.970) and upper anterior (86.7–90.2%; 0.948–0.958) and lower (85.6–87.2%; 0.913–0.937) and upper posterior teeth (78.1–81.0%; 0.851–0.875). In this study, only minor differences among the tested networks were detected for PBL detection. To increase the diagnostic performance and to support the clinical use of such networks, further optimisations with larger and manually annotated image data sets are needed.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Abstract Background Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs. Methods Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) on Day 0. All dogs were infested with approximately 100 unfed, adult fleas (C. felis or C. canis) prior to treatment and weekly for 5 weeks post-treatment. In Studies 1, 2 and 3, the number of viable fleas were comb-counted at 24 h after treatment and after each weekly infestation; Study 2 also included groups treated with tablets containing sarolaner-alone (1.2 mg/kg), moxidectin-alone (24 µg/kg) or pyrantel-alone (5 mg/kg). In Study 4, flea counts were conducted at 3, 4, 8 and 12 h after treatment and subsequent weekly infestations to establish speed of kill. In Study 5 (flea reproduction), dogs were housed in an enclosure designed to facilitate collection of flea eggs. Results Efficacy of Simparica Trio™ against C. felis was ≥ 99.7% and against C. canis was 100% at 24 h after treatment and after subsequent infestations for at least 35 days. Treatment with sarolaner-alone had similar efficacy to Simparica Trio™, while moxidectin-alone and pyrantel-alone were no different from placebo at most time points. In Study 4, significant flea killing started at 4 h after treatment; by 8 h after treatment, all treated dogs were free of fleas. Following weekly re-infestation, the combination product reduced fleas by ≥ 97.8% within 12 h for 28 days. Simparica Trio™ reduced flea egg-laying by 100% for 35 days. No treatment-related adverse reactions occurred in any study. Conclusions A single dose of Simparica Trio™ at the recommended minimum dose provided highly efficacious and rapid treatment within 4 h of existing flea infestations and persistent control of fleas on dogs for 5 weeks. The efficacy against fleas resulted in 100% prevention of flea reproduction for over a month following a single oral dose.

Abstract Background Ancylostomatids (‘hookworms’) are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adult A. caninum, and adult U. stenocephala infections in dogs. Methods Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. Results Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4 larval stage of A. caninum, ≥ 99.8% against immature adult (L5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. Conclusions These studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4 larval and immature adult (L5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.

Abstract Background Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs. Methods Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7–10 days after treatment compared to placebo control. Results Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. Conclusions These studies confirm the efficacy of a single dose of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.

The incidence and prevalence of valvular heart disease (VHD) is increasing and has been described as the next cardiac epidemic. Advances in imaging and therapeutics have revolutionized how we assess and treat patients with VHD. Although echocardiography continues to be the first-line imaging modality to assess the severity and the effects of VHD, advances in cardiac computed tomography (CT) now provide novel insights into VHD. Transcatheter valvular interventions rely heavily on CT guidance for procedural planning, predicting and detecting complications, and monitoring prosthesis. This review focuses on the current role and future prospects of CT in the assessment of aortic and mitral valves for transcatheter interventions, prosthetic valve complications such as thrombosis and endocarditis, and assessment of the myocardium.

Izhodišče: Ocena razširjenosti raka endometrija pred operaciji s slikovnimi metodami ni zanesljiva. Od ocene je odvisno, ali naj kirurško zdravljenje vključuje pelvično limfadenektomijo ali ne. Biopsija varovalne bezgavke lahko varno nadomesti radikalno pelvično limfadenektomijo pri bolnicah z nizkim in zmernim tveganjem za ponovitev bolezni. Metode: Od januarja 2016 do junija 2017 je bilo na Ginekološki kliniki v Ljubljani v pregled začetnih kliničnih rezultatov ob uvedbi biopsije v varovalni bezgavki v rutinsko klinično prakso vključenih 35 bolnic. Beležili smo zanesljivost histološke in ultrazvočne ocene pred operacijo ter stopnjo uspešne kirurške detekcije v varovalni bezgavki s cervikalno aplikacijo zelenila indocianin. Vsa odstranjena tkiva so bila poslana na histološko preiskavo z barvanjem po metodi hematoksilin in eozin (H&E). Rezultati: Enostranska uspešnost kirurške detekcije varovalne bezgavke je bila 85,7 % (75–93 %), obojestranska pa 80,0 % (63–92 %). Varovalna bezgavka je bila histološko pozitivna v dveh primerih. Ultrazvočna ocena invazije v miometrij je imela občutljivost 100 % (15,8–100 %) in specifičnost 78,9 % (54,4–93,9 %), ultrazvočna ocena invazije v stromo materničnega vratu pa le 33 % (0,8–90,6 %) občutljivosti in 94,4 % (72,7–99,8 %) specifičnosti. Ocena histološke stopnje diferenciacije je bila po operaciji višja (angl. upgrading) v 5,7 %, nižja (angl. downgrading) pa v 8,6 %. Zaključek: Odstranjevanje varovalne bezgavke omogoča individualnejši pristop k zdravljenju bolnic z rakom endometrija in varnejšo opustitev pelvične limfadenektomije pri bolnicah z nizkim in zmernim tveganjem za ponovitev bolezni. Za dokončno umestitev v smernice zdravljenja bodo v našem prostoru potrebne dodatne izkušnje glede izbire bolnic, sledenja kakovosti kirurške obravnave in nujna uvedba res poadrobnega histološkega pregleda – t. i. ultrastaginga (angl. ultrastaging) odstranjene varovalne bezgavke.

ni abstrakta

Background: The COVID-19 pandemic threatens the impact of cervical cancer screening and global cervical cancer elimination goals. As cervical cancer screening programmes were adjusting to the new situation, we evaluated the intensity, quality, and outcomes of cervical cancer screening in Slovenia in the first seven months of the pandemic. Methods: Historical observational study on data from a population-based cervical cancer screening registry. Number of cervical cytopathology (screening and follow-up), histopathology (diagnostic procedures, invasive procedures and number of newly diagnosed CIN2+ cases) and HPV test results from the entire Slovenian women population between January 1st and September 30th 2020 were compared to a three-year average of the years 2017–19. Findings: A two-month screening lock-down between March 12th and May 8th 2020 resulted in an epidemic deficit of screening (-92%), follow-up (-70%), and HPV triage tests (-68%), as well as invasive diagnostic (-47%) and treatment (-15%) of cervical lesions. Time to diagnosis and treatment did not increase; times to laboratory results fluctuated but stayed within standards. Slovenia has entered the second epidemic intending to add as little as possible to the pandemic deficit of screening smears (-23%) and yearly CIN2+ cases (-10%). Women aged 30–39 were most affected, with the highest pandemic deficit of screening smears (-26%) and yearly CIN2+ cases (-19%). Interpretation: The pandemic has deeply affected all levels of our lives. New vulnerable groups and inequalities have emerged that require recognition and action. To prevent long-term increases in the cervical cancer burden due to the COVID-19 pandemic, it is crucial that organised screening is maintained and monitored in settings where it can be safely and comprehensively provided. Funding: None.

Abstract Background Canine demodicosis is classified as localised or generalised according to the extent of the disease. Chronic generalised demodicosis is a difficult skin disease to treat and unlikely to resolve without therapy. This laboratory study compared the efficacy of two topical spot-on medications, fluralaner or a combination of imidacloprid and moxidectin, against naturally acquired generalised demodicosis in dogs. Methods Sixteen client-owned dogs with naturally acquired generalised demodicosis were randomly allocated to 1 of 2 study groups consisting of 8 dogs each. On Day 0, dogs in 1 group were treated once with fluralaner spot-on solution. Dogs in the other group were treated with the imidacloprid/moxidectin spot-on solution on 3 occasions (Days 0, 28 and 56) or weekly in severe cases. Mites were counted in skin scrapings and demodectic lesions were evaluated on each dog before treatment, and at 28-day intervals over the 12-week period. Deep skin scrapings were made from the same 5 sites on each dog at each examination. Results After administration of fluralaner, miticidal efficacy was 99.7% at Day 28, > 99.9% at Day 56 and 100% at Day 84. Efficacy in dogs treated topically with the imidacloprid and moxidectin combination, was 9.8% at Day 28, 45.4% at Day 56 and 0% at Day 84, and was significantly (P < 0.01) lower than the fluralaner treated group at each post-treatment time point. Conclusions A single topical administration of fluralaner eliminated Demodex sp. mites on dogs with generalised demodicosis. Topical imidacloprid/moxidectin combination treatment administered 3 times at 28-day intervals, or more frequently, did not eliminate mites from most treated dogs.

Abstract Background Dipylidium caninum is a common tapeworm of dogs contracted from ingestion of fleas containing the infective cysticercoid stage. Fluralaner is a systemically distributed isoxazoline class insecticide that delivers highly effective activity against fleas and ticks for up to 12 weeks after a single oral or topical treatment. This study evaluated the impact of this flea insecticidal efficacy on the transmission of D. caninum to dogs. Methods Dogs were weighed and treated with a cestocide and then randomly assigned to 3 groups of 8. Fluralaner was administered topically (at the commercial dose) to one group and orally to another group while the third received topically administered sterile water. All dogs were subsequently infested with about 100 D. caninum infected Ctenocephalides felis at 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 and 83 days after treatment. Visual proglottid inspections and counts were conducted daily from 35 to 113 days post-treatment. Post-treatment D. caninum incidence was calculated for each group and compared between treated and untreated groups. Results All 8 dogs in the placebo-treated group became infected with D. caninum while no shed proglottids were observed at any point during the post-treatment period from any dog in either fluralaner treated group. Conclusions The insecticidal efficacy of a single treatment of either orally or topically administered fluralaner prevented D. caninum transmission from infected fleas to susceptible dogs for up to 12 weeks following administration.

Abstract Positron emission tomography (PET) and magnetic resonance imaging (MRI) have both been used for decades in cardiovascular imaging. Since 2010, hybrid PET/MRI using sequential and integrated scanner platforms has been available, with hybrid cardiac PET/MR imaging protocols increasingly incorporated into clinical workflows. Given the range of complementary information provided by each method, the use of hybrid PET/MRI may be justified and beneficial in particular clinical settings for the evaluation of different disease entities. In the present joint position statement, we critically review the role and value of integrated PET/MRI in cardiovascular imaging, provide a technical overview of cardiac PET/MRI and practical advice related to the cardiac PET/MRI workflow, identify cardiovascular applications that can potentially benefit from hybrid PET/MRI, and describe the needs for future development and research. In order to encourage its wide dissemination, this article is freely accessible on the European Radiology and European Journal of Hybrid Imaging web sites. • Studies and case-reports indicate that PET/MRI is a feasible and robust technology. • Promising fields of application include a variety of cardiac conditions. • Larger studies are required to demonstrate its incremental and cost-effective value. • The translation of novel radiopharmaceuticals and MR-sequences will provide exciting new opportunities.

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We investigate synchronization patterns and chimera-like states in the modular multilayer topology of the connectome of Caenorhabditis elegans. In the special case of a designed network with two layers, one with electrical intra-community links and one with chemical inter-community links, chimera-like states are known to exist. Aiming at a more biological approach based on the actual connectivity data, we consider a network consisting of two synaptic (electrical and chemical) and one extrasynaptic (wireless) layers. Analyzing the structure and properties of this layered network using Multilayer-Louvain community detection, we identify modules whose nodes are more strongly coupled with each other than with the rest of the network. Based on this topology, we study the dynamics of coupled Hindmarsh-Rose neurons. Emerging synchronization patterns are quantified using the pairwise Euclidean distances between the values of all oscillators, locally within each community and globally across the network. We find a tendency of the wireless coupling to moderate the average coherence of the system: for stronger wireless coupling, the levels of synchronization decrease both locally and globally, and chimera-like states are not favored. By introducing an alternative method to define meaningful communities based on the dynamical correlations of the nodes, we obtain a structure that is dominated by two large communities. This promotes the emergence of chimera-like states and allows to relate the dynamics of the corresponding neurons to biological neuronal functions such as motor activities.

Abstract Background Fluralaner is a novel systemic ectoparasiticide for dogs and cats providing immediate and persistent flea- and tick-control after a single topical dose. Prescribing directions recommend waiting 72 h following topical administration before immersing dogs in water. The objective of this study was to determine whether water immersion immediately prior to treatment or earlier than 72 h post-treatment reduced subsequent treatment efficacy. Methods Forty (n = 40) dogs were blocked on tick carrying capacity into 5 experimental groups and all but one of the groups (untreated control) were treated topically with fluralaner (Bravecto® Spot-On Solution, Merck Animal Health, Madison, NJ, USA) at the commercial dose. Three of the four remaining groups were immersed in 38–40 °C water for a 5 min bath - either 1 h before treatment; 12 h after treatment; or 24 h after treatment. Seven days after treatment all dogs were challenged with 50 Rhipicephalus sanguineus (sensu lato) ticks and after 24 h attached ticks were counted and removed. Results Efficacies (compared to the untreated control group) were: 99.3% for no water immersion; 99.6% for immersion 1 h before treatment; 99.3% for immersion 12 h after treatment; and, 100% for immersion 24 h after treatment. Conclusions Water immersion of dogs around the time of topical fluralaner administration did not reduce subsequent systemic acaricidal efficacy.

Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne viruses, such as Powassan virus and tick-borne encephalitis virus, are transmissible within 15–60 min after tick attachment. However, a minimum of 3–24 h of tick attachment is necessary to effectively transmit bacterial agents such as Ehrlichia spp., Anaplasma spp., and Rickettsia spp. to a new host. Longer transmission periods were reported for Borrelia spp. and protozoans such as Babesia spp., which require a minimum duration of 24–48 h of tick attachment for maturation and migration of the pathogen. Laboratory observations indicate that the probability of transmission of tick-borne pathogens increases with the duration an infected tick is allowed to remain attached to the host. However, the transmission time may be shortened when partially fed infected ticks detach from their initial host and reattach to a new host, on which they complete their engorgement. For example, early transmission of tick-borne pathogens (e.g., Rickettsia rickettsii, Borrelia burgdorferi, and Babesia canis) and a significantly shorter transmission time were demonstrated in laboratory experiments by interrupted blood feeding. The relevance of such situations under field conditions remains poorly documented. In this review, we explore parameters of, and causes leading to, spontaneous interrupted feeding in nature, as well as the effects of this behavior on the minimum time required for transmission of tick-borne pathogens.

Background: Morbidity and mortality caused by cancer persist to be an important health problem world- wide and in the European Union member states as well. In Slovenia, most ovarian cancer cases are detected in advanced stages, hence a rather high mortality rate. Aims: The purpose of this research project is to analyze the primary cytoreduction in the patients with advanced ovarian cancer. The main objective of the project is to assess the use of lap- aroscopy in the prediction of optimal cytoreduction in these patients. Applicative research project ‘Estimation of survial in patients with advanced ovarian can- cer based on primary laparoscopical assessment of optimal cytoreduction’ (L3-2371) was approved and has been financed by the Slovene Research Agency and co-financed by the Ministry of Health of RS; Duration: May 1, 2009–April 30, 2012. Methods: The research project will consist of retrospective and prospective study. In all the patients with advanced ovarian cancer managed at the Department of Obstetrics and Gynecol- ogy, University Medical Centre Ljubljana in the years 2003–2008, and in whom optimal primary cytoreduction was made using either laparoscopy or laparotomy, certain clinical and pathomorphological factors will be compared, and the effects of all analyzed factors on the outcome of treatment assessed. In the prospective study, we will aim at assessing the use of laparoscopy in the prediction of optimal cytoreduction in all newly detected cases using a laparoscopy-based score (Fagotti’s scoring system). Conclusions: The standard management of advanced ovarian cancer patients consists of primary surgical optimal and/or suboptimal cytoreduction followed by aggressive cytotoxic chemotherapy. In line with our experience and with that published most recently, laparoscopy seems to be a promising method with which we will attempt to most accurately assess the optimal cytoreduction in surgical treatment of ovarian cancer patients.

Eight enzyme systems coding for 14 loci were assayed in Juniperus phoenicea. Mendelian inheritance was confirmed for allozymes at 10 loci (Fle 2, Gdh, Got 1, Idh, Mdh 1, Mdh 2, Men 1, Pgi, Pgm I, Pgm 2) by testing the fit of band-pattern segregation in macrogametophytes from heterozygous trees to the expected I: I ratio. Linkage relationships were examined for 21 pairs of allozyme loci and these pairs do not appear to be linked in our material.

The isoenzyme variation in a geographically well isolated population of Juniperus oxycedrus subsp. macrocarpa from Korfu island was investigated. Based on the 18 putative isoenzyme loci a very low level of variation has been observed. In the studied material only 11% (95% criterion) of the loci were polymorphic. The number of alleles per locus was 1.17 and the observed, and expected heterozygosities were 0.016, and 0.024, respectively.

In Białowieża Primeval Forest, in 1823 Stanisław Górski discovered on the Cisovka Hag, a relic population of European silver-fir (Abies alba Mill.). This population is isolated and most away, 120 km to the North-East, from the border of European-silver-fir distribution. Besides the natural population Cisovka, there are also man-made silver fir stands and clumps in the Polish and Belorussian part of Białowieża Primeval Forest. In the Polish part there are four such artificial stands. If the seed-producing silver-fir stands really originated from the Cisovka population, then they are a very valuable part of the declining population and an easy accessible seed source. However, if these populations were introduced to the Białowieża Primeval Forest, then they are a potential source of dangerous genetic pollution of the Cisovka population. The relationship of the genetic structure of the Cisovka population to man-made silver-fir-stands in Białowieża Forest was investigated with the help of 17 loci of 1 1 enzyme systems. Genetic diversity of Cisovka population is characterized by the smallest mean number of alleles per locus (Mal= 1.353, includes all loci studied and per polimorphic locus Malp = 2.00). In Cisovka population there is very low-grade of polimorphic loci (Pp = 11.765 with the mean 37.255 for all studied populations). Expected heterozygosity, He = 0.079 revealed very low-grade of genetic diversity in the population. The observed heterozygosity (Ho = 0.123) was similar to this characterictic in other populations. A dendrogram based on Neis genetic distance coefficient (D) among 9 silver-fir populations was constructed. Cisovka in the UPGMA dendrogram is a distinct population separated from other ones by a very great genetic distance (D = 0.06). Also two man-made silver-fir (B I and 132) stands are separated from others. Only populations B3 and B4 are combined into one subgroup linked to the population Tomaszów Lubelski. Basing on the received results one should decide that all the four studied artificial stands were introduced to Białowieża Primeval Forest from beyond of this geographical regions. There is some reason to assume (on the GDH2 allele frequency) that man-made silver-stands in compartments 453Aa and 498Cg are of eastern provenance. It is rather certain that these stands are not of offspring of Cisovka populations.

The action of fluorides and sulphur dioxides from emissions from a phosphate fertilizer factory significantly reduced the germination of Scots pine pollen grains. The pollen tube length indicated that its growth is uninhibited even though the pollen was collected under conditions of air-pollution. There are statistically significant differences showing longer tubes in the sensitive trees pollen grains. l he ageing of pollen from the sensitive trees occurs probably more rapidly than in the tolerant trees.

The purpose of this study is to analyse the current activities of Norwegian ambulatory rehabilitation teams at a time when the field of rehabilitation is set for major changes with the recent introduction of the new pro-rehabilitation Coordination Reform. The content of the all logged consultations of four ambulatory teams belonging to one of the four regional health authorities was analysed in terms of municipality population size and, where possible, the age-distribution of the patients. Consultations were coded into one of four main codes, i.e. 'investigation and diagnostics; treatment and practical training; consultation, collaboration and training; and auxiliary measures'. A total of 2992 consultations were registered for period 2009–2012, with the far majority of consultations involving patients aged =67 years, and the elderly under-represented in especially the smaller municipalities. Analysis showed differential rehabilitation activity towards the elderly in the two rehabilitation teams which registered the far majority of consultations, which were also concentrated in only three of the 18 sub-codes. Provision of rehabilitation seems to lack an overall coordinating strategy. The kind and level of rehabilitation any given elderly person is entitled to, by and large, depends on the place of residence of the patient.

BackgroundThe second most common cancer in women up to 65 years of age is cervical cancer. Same cancer is the leading cause of death from gynaecological deseases worldwide.The standard procedure for cervical cancer treatment with FIGO stage including IB2 is radical hysterectomy sec. Wertheim-Meigs-Novak with or without adnexa with radical pelvic lymphadenectomy and/or para-aortic lymphadenectomy. In the last two decades has with the development of laparoscopy also developed laparoscopic radical hysterectomy .Laparoscopic radical hysterectomy with pelvic and para-aortic lymph nodes dissection was performed for the first time by Nezhat with coworkers in 1989.Laparoscopic radical hysterectomy with pelvic and/or paraaortic lymphnode dissection in treatement of cervical cancer including FIGO stage IB1 is performed at Dep Ob/Gyn UKC Ljubljana since 2013. The purpose of this article is to evaluate the morbidity and safety of the procedure. MethodsWe retrospectively reviewed the medical records of patients with cervical cancer who underwent laparoscopic radical histerectomy with pelvic and/or paraaortic lymphadenectomy from April 2013 to May 2016. Results34 patient were included, 32 patients with CC FIGO stage IB1, 1 patient with CC FIGO stage IB2, 1 patient with CC FIGO stage IIB.There were four (11,8%) bladder lesions, all of them were corrected during the surgery, but no ureteral lesion! There was one (2,9%) surgical revision right after the surgery due to assumption of bleeding (though there was no active bleeding found).Three patients (8,8%) had permanent urinary dysfunction – retention. One patient (2,9%) had dehiscence of vaginal vault after 4 months (after sexual intercourse)There was no ureterovaginal/vesicovaginl fistula after surgery! The mean operating time was 2 hours 55 min, mean admission time after surgery was 8,7 days, mean blood loss during operation was 291 ml. ConclusionsLaparoscopic radical hysterectomy is the method of choice in cervical tumors including FIGO stage IB1.Percentage of bladder lesions is part of learning curve.Our goal in future is to decrease the percentage of bladder lesions and to decrease the percentage of patients suffering from bladder dysfunction by using „nerve sparing“ technic.We expect, the same results for 5 year survival rate as with patients treated with classical radical hysterectomy.

Seeds collected from individual trees in the 16 Carpathian and 2 Sudeten silver-fir (Abies alba) populations were studied with the starch gel electrophoresis in megagametophytes using 14 enzyme systems with 28 loci. The results show that the geographical distance between populations are in a small part reflected in genetic distances. There are two main groups of populations: Sudeten and Carpathian with a very big genetic distance between them. Other populations consist of a few small groups with low gene flow between them (Nm = 3.286). About 80% of genetic variation is located within populations (FST = 0.223). Average values for genetic multiplicity and diversity for Carpathian populations are as follows: number of alleles per locus: Na = 2.308, with effective number of alleles Ne = 1.552 and proportion of polymorphic loci 71.21%. The mean number of alleles per locus (Na) varied from 2.107 to 2.607 in population. The mean effective number of alleles per locus (Ne) ranged from 1.429 to 1.662. Average Fis for Carpathian populations was -0.021, which means that there is small excess of heterozygotes. The average observed heterozygosity amounted to Ho = 0.275 and expected heterozygosity was He = 0.269. The dendrogram structure and presence of rare alleles found in silver-fir of Czech, and Slovakian populations allow for a hypothesis that in postglaciation the silver-fir moved into the Polish Carpathians not westward from the east but from the south along river valleys from some Balkan refuges, getting North bypassing the High Tatra Range. This way, a highly diversified set of populations originated, differ in the presence of rare alleles. This differentiation is not prevented by a relatively small flow of genes between populations. The calculated gene flow Nm = 3.286 also indicates isolation between the populations. It means 3.3 immigrants per generation into the studied populations.

With the help of 21 putative isoenzyme loci, the genetic diversity and variations of Viscum album ssp. album L. from 42 species, subspecies, varieties and hybrids of broadleaf trees, Viscum album ssp. austriacum (Wiesb.) Vollmann, from 4 populations of Scots pine (Pinus sylvestris L.) and Viscum album ssp. abietis (Wiesb.) Abromeit, from 8 populations of European silver fir (Abies alba Mill.) were analyzed. On the dendrogram, the three investigated subspecies form three clusters, each clearly separated from the other, so we suggest a revision of the systematic nomenclature proposed to take into consideration a return to an earlier system of dividing the European mistletoe into three species: Viscum album L., Viscum abietis Beck, and Viscum laxum Boiss. et Reut. From among the 21 tested loci only one locus, SOD-A, was monomorphic. The average number of actual alleles (Na) and effective alleles (Ne) was 2.23 and 1.61 respectively. The observed heterozygosity (Ho) varied from 0.199 in V. album ssp. abietis to 0.345 in the V.a. ssp. album populations. Average FST = 0.277 indicates that about 28% of genetic differentiation is due to an interpopulation diversity of Viscum album populations. There is a small gene flux between Viscum album populations with only one immigrant successfully entering a population per two generations (Nm = 0,653).

Twenty-eight isozymic loci were studied in the Beskid Mts., in four populations of common silver-fir (Abies alba): one in Beskid Makowski (BM) and three populations in Beskid Sądecki (BS). Their genetic variation and diversity were analyzed, and Nei's genetic distances between the populations were calculated. The results show that the geographical distance between the BM population and the three BS populations is reflected in genetic distances. The BM population is clearly distinct from the others. It has the lowest genetic diversity (I = 0.42), percentage of polymorphic loci (%PoL = 64.29) and number of rare alleles (NoRa = 5). Besides, the BM population has the highest observed heterozygosity (Ho = 0.291), which exceeds the expected heterozygosity (He = 0.254), estimated on the basis of the Hardy-Weinberg Principle. On the contrary, BS populations are in the state of equilibrium, which is manifested, in similar values of He = 0.262 and Ho = 0.264.

To assess the inter- and intrapopulation genetic variation in the filial generation (F1) of alder (Alnus glutinosa (L.) Gaertn.), 11 naturally regenerated populations were analysed. Their parental populations (P), represent the whole Polish territory and belong to three phytosociological associations with alder: typical alder swamp forest Carici elongatae-Alnetum (Ce-A); alder riparian forest Circaeo-Alnetum (C-A); and ash-elm riparian forest Fraxino-Ulmetum (F-U). F1 populations are grown in a common-garden experiment (provenance trial). Genotyping of individual trees has been carried out by analysis in a bud tissue allele frequency in the 21 isozyme putative loci of 10 enzymes. Differences between populations in respect to the level of genetic diversity were not high. Genetic diversity measured as the number of effective alleles per locus was the highest (Ne = 1.65) in population Wińsko originating from F-U (where also the inbreeding coefficient was the highest, F = 0.429), and the lowest (Ne = 1.48) in population Sławki from Ce-A. In all investigated populations, observed heterozygosity (Ho = 20%) was lower than expected from H-W equilibrium (He = 29%). The highest genetic variation expressed as percentage of polymorphic loci (77.3%) was observed in the offspring populations from Ce-A, and the smallest (69.9%) in the populations originating from F-U. It seems that the low genetic differentiation between populations is probably connected with long-distance seed dispersal via river systems. Alder seed can be transported over long distances thanks to periodical flooding. There is some gene flow between alder populations, with about 2.5 immigrants successfully entering a population per generation (Nm = 2.55). The level of population subdivision within A. glutinosa was low (Fst = 0.089). There was no significant genetic differentiation between populations from different phytosociological associations. Mantel test exhibited no significant correlation (r = 0.077) between genetic and geographic distance. In the dendrogram constructed according to Nei (1972) on the basis of interpopulation genetic distances, many small groups can be observed.

Annual plant species were found to have several distinct classes of hexokinases which are specific for different hexoses, such as glucose, fructose and mannose. In conifers one isozyme of hexokinase could be found in genetic studies if only glucose was employed as substrate. If fructose was substituted for glucose, another isozyme zone different from the common hexokinase could be observed in zymograms of extracts from seed tissues of Norway spruce, Scots pine and silver fir. Hence these three conifer species possess at least two different hexokinases, glucokinase and fructokinase.

Background: Initial surgical debulking followed by a systemic chemotherapy is the standard treatment sequence for advanced ovarian cancer (AOC) treatment. The purpose of this article is to evaluate prognostic factors that impact the success of AOC treatment. Methods: All patients with AOC (FIGO stage III and IV) who were surgically treated at the Division of Gynaecology, University Medical Centre of Ljubljana, in the period from 2003 to 2008 and further received cytotoxic chemotherapy at the Institute of Oncology in Ljubljana were included in this retrospective study. Women with advanced borderline ovarian cancer and patients who initially received neoadjuvant chemotherapy and those whose adjuvant chemotherapy was not platinum-based were excluded from the analysis. Results: A total of 159 women were enrolled in the study, while data were analyzed for 116 patients. Their median age was 59 years (23–80 years) and did not have a significant influence on the treatment outcome. Clear-cell histological type of AOC was an important risk factor for a disease-free interval (DFI) (HR = 2.41, CI 95 % 0.9–5.9; p = 0.08) and overall survival (OS) (HR 4.045; 95.0 % CI 1.5–10.6; p = 0.003). Postoperative residual tumour larger than 2 cm represented a statistically independent risk factor for poor OS. Residual tumour in the upper abdomen did not represent a statistically significant risk factor either for DFI (HR = 1.93; CI 95 % 0.9–4.06; p = 0.08) or for OS (HR = 1.47; 95.0 % CI 0.5–3.8; p = 0.491). Median follow up time was 29.5 months, median DFI 18 months (95 % CI 16– 20) and median OS 32 months (95 % CI 22–42). 74 (63.8 %) patients died. Conclusion: Clear-cell histological type of AOC and residual tumour larger than 2 cm are the most important risk factors for early progress of the disease and poor OS. Hence improvement of surgical treatment is crucial for better treatment outcomes for patients with AOC. The latter can be achieved by an interdisciplinary surgical approach.

Background. Nowadays, endometrial cancer is the most frequent gynecologic malignancy with a relatively good prognosis. The prognosis and the quality of life of these patients can be improved considering the prognostic factors and more rational treatment.Methods. This retrograde analysis comprised 499 patients with endometrial cancer operated at the Department of Obstetrics and Gynecology and then irradiated at the Institute of Oncology in Ljubljana in the period 1995–1999.Results. Most patients had stage I disease (81.4%), good prognostic histological type (endometroid and adenoacanthoma in 81.3%), well- and moderately differentiated tumors (86%) and early myometrial invasion (72.4%). In the observed period we performed radical hysterectomy »old« Wertheim (Piver II) in only 8.4% of cases, in all other cases simple vaginal or abdominal hysterectomy (in 46.9% with pelvic lymphadenectomy) was done. Adjuvant irradiation was administered to 70% of patients. The analysis of 3- and 5-year survival comprises only 466 patients. The overall 5-year survival was 85.8%, in stage I cases 88.1%. There were no significant differences in survival in stage I cases regarding the type of surgery. In stage I the most important adverse prognostic factors were poor differentiation, deep myometrial invasion and serous-papillary histologic type, whereas lymph node involvement was very rare (less than 1%).Conclusions. For the choice of appropriate surgical treatment of patients with endometrial cancer it is necessary to consider the prognostic factors. In this analysis a more radical surgical procedure did not improve the survival significantly. The usefulness of limphadenectomy in stage I remains open.

Background. Traditional surgical technique applied in the treatment of endometrial carcinoma is total abdominal hysterectomy combined with bilateral salpingooophorectomy. Laparoscopic surgical technique, providing the possibility of simultaneous hysterectomy and lymphadenectomy through the vagina, represents the alternative to laparotomy. The objective of this analysis was to evaluate periand postoperative parameters of both techniques, and the appropriateness of the number of removed nodes.Methods. This retrospective comparative analysis involved 36 patients (Group LAVH), who underwent laparoscopic surgical treatment for stage I endometrial carcinoma in the period 1995–2003, and 24 randomly chosen patients (Group TELA), in whom the same surgical procedures were performed using abdominal approach. The data for comparison of general clinical parameters, duration of surgery, blood loss, early and late postoperative complications, duration of stay at the intensive care unit and hospital stay, were collected from the operative and anesthesiology records. Histologic findings provided histopathomorphologic data on carcinoma and the number of removed nodes. The comparison of all parameters was evaluated using Student T-test for continuous variables, and Chi-square test and Mann-Whitney test for categorical variables.Results. General clinical parameters and the patient age were evenly distributed between the groups. The same applies for the distribution of mean blood loss and early postoperative complications. Two patients, treated laparoscopically, were re-admitted to hospital for pelvic abscess. The mean duration of stay at the intensive care unit was longer in the TELA group patients (3.3 ± 1.1) than in the LAVH group patients (2.1 ± 0.45) (F = 30.41; p < 0.0001). Also, most patients from the LAVH group were discharged from hospital on day 8 after surgery (8.47 ± 2.3 days), and on day 11 in the TELA group (11.7 ± 3.4 days) (F = 17.46; p < 0.0001). In the LAVH group mean 18 ± 6 nodes were removed, and in the TELA group 14 ± 8, the difference being statistically significant (p = 0.03).Conclusions. Although this analysis was retrospective, the obtained results confirm the findings of other authors regarding the advantages offered by the laparoscopic technique, the most important being hysterectomy combined with salpingo-oophorectomy performed through the vagina, quicker postoperative recovery and satisfactory surgical staging for stage I endometrial cancer.

En este trabajo resumimos las técnicas más habituales que permiten diagnosticar las causas de infactibilidad de programas con restricciones lineales. Además, presentamos dos métodos que, con las mínimas transformaciones posibles del modelo inicial, permiten hacer viable un programa infactible. Los métodos descritos son aplicados a un modelo de selección de carteras eficientes.

Obesity is a pandemic currently affecting the world's population that decreases the quality of life and promotes the development of chronic non-communicable diseases. Lactobacillus rhamnosus is recognized for multiple positive effects on obesity and overall health. In fact, such effects may occur even when the microorganisms do not remain alive (paraprobiotic effects). This raises the need to elucidate the mechanisms by which obesity-associated factors can be modulated. This narrative review explores recent findings on the effects of L. rhamnosus , particularly, its postbiotic and paraprobiotic effects, on the modulation of adiposity, weight gain, oxidative stress, inflammation, adipokines, satiety, and maintenance of intestinal integrity, with the aim of providing a better understanding of its mechanisms of action in order to contribute to streamlining its clinical and therapeutic applications. The literature shows that L. rhamnosus can modulate obesity-associated factors when analyzed in vitro and in vivo. Moreover, its postbiotic and paraprobiotic effects may be comparable to the more studied probiotic actions. Some mechanisms involve regulation of gene expression, intracellular signaling, and enteroendocrine communication, among others. We conclude that the evidence is promising, although there are still multiple knowledge gaps that require further study in order to fully utilize L. rhamnosus to improve human health.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Background and Aims: Ambrosia arborescens Mill. ( A. arborescens ) is an aromatic plant used in traditional medicine as an anti-inflammatory, anti-tussive, anti-rheumatic, and anti-diarrheal agent. This study aimed to evaluate the effect of A. arborescens Mill. on a Rattus norvegicus var. albinus -induced breast cancer model., Materials and Methods: We collected A. arborescens from the province of Julcán, La Libertad Region, Per, and prepared an ethanolic extract using pulverized leaves macerated in 96° ethanol for 72 h with magnetic stirring. In the evaluation of anticancer activity, four experimental groups with 10 female rats each were formed: Group I (Control-7,12-dimethylbenz[a]anthracene [DMBA]), which received DMBA (single dose) and physiological saline solution for 4 months, and Groups II, III, and IV, which received DMBA (single dose) and 200, 400, and 600 mg/kg/day of the ethanolic extract of A. arborescens , respectively, for 4 months., Results: The DMBA control group presented histological characteristics of ductal carcinoma in situ with necrotic and inflammatory areas, whereas the A. arborescens extract group showed a decrease in tumor volume and recovery of the ductal duct., Conclusion: Ethanol extract of A. arborescens leaves decreases tumor development in rats with induced breast cancer, and this effect is dose-dependent., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Silva-Correa, et al.)

Species with extensive geographical ranges pose special challenges to assessing drivers of wildlife disease, necessitating collaborative and large-scale analyses. The imperilled foothill yellow-legged frog ( Rana boylii ) inhabits a wide geographical range and variable conditions in rivers of California and Oregon (USA), and is considered threatened by the pathogen Batrachochytrium dendrobatidis (Bd). To assess drivers of Bd infections over time and space, we compiled over 2000 datapoints from R. boylii museum specimens (collected 1897-2005) and field samples (2005-2021) spanning 9° of latitude. We observed a south-to-north spread of Bd detections beginning in the 1940s and increase in prevalence from the 1940s to 1970s, coinciding with extirpation from southern latitudes. We detected eight high-prevalence geographical clusters through time that span the species' geographical range. Field-sampled male R. boylii exhibited the highest prevalence, and juveniles sampled in autumn exhibited the highest loads. Bd infection risk was highest in lower elevation rain-dominated watersheds, and with cool temperatures and low stream-flow conditions at the end of the dry season. Through a holistic assessment of relationships between infection risk, geographical context and time, we identify the locations and time periods where Bd mitigation and monitoring will be critical for conservation of this imperilled species., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Background: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic., Methods: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere., Findings: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories., Interpretation: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies., Funding: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization., Competing Interests: Declaration of interests The UK Health Security Agency's Immunisation and Vaccine Preventable Diseases Division has provided vaccine manufacturers (GSK, Pfizer, and Sanofi) with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. The UK Health Security Agency's Respiratory and Vaccine Preventable Bacteria Reference Unit has received unrestricted research grants from Pfizer to participate in pneumococcal surveillance projects. CHI de Créteil (France) received research grants from the French Public Health Agency, Pfizer, and MSD. University Hospitals Leuven (Belgium) received research grants from Merck-MSD and Pfizer, and consulting fees from Merck-MSD. SD received personal payments or honoraria from Pfizer. The Swiss National Reference Center for Invasive Pneumococci received funding from the Federal Office of Public Health. MH has received grants from Pfizer and personal fees (for being on an advisory board) from Pfizer and Merck Sharp & Dohme. The National Medicines Institute (Warsaw, Poland) received funding from the Polish Ministry of Health, the Polish Ministry of Science and Higher Education, Pfizer, and MSD. AS received payments from MSD and Pfizer for lectures, and from MSD, Pfizer, and Sanofi Pasteur for participation in advisory boards. AS is the unpaid Vice President of the European Meningococcal and Haemophilus Disease Society. The Finnish Institute for Health and Welfare (Finland) received research funding from Pfizer. ABB is an unpaid adviser to WHO, providing expertise related to vaccines and antimicrobial resistance. ABB is an unpaid General Assembly member (2022 onwards), and has been a board member (2016–22) and Secretary (2018–22), of the International Society of Pneumonia and Pneumococcal Diseases (ISPPD). MD has received financial support from Pfizer to attend national scientific meetings. MdP received grant funding from the National Research Foundation (South Africa) and the Bill & Melinda Gates Foundation to support the International Pathogenic Neisseria Conference (IPNC) 2022 meeting. MdP received personal support from the ISPPD to participate in the ISPPD conference in 2022, and was a member of the organising and scientific committee for the IPNC meeting in 2022. HH and MC received a grant from Pfizer (W1243730) to investigate Irish pneumococcal serotypes by whole-genome sequencing. HH received payment from Scottish Hospitals Enquiry for expert testimony. HH was the President of the Healthcare Infection Society (2018–22). KAJ received personal royalties from GlaxoSmithKline, and personal honoraria from the Wellcome Trust. SL performs contract research on behalf of St George's University of London for pharmaceutical companies (GlaxoSmithKline, Pfizer, and Sanofi), including vaccine manufacturers, but does not receive any personal remuneration. T-TL received consulting fees from the Trond Mohn Foundation. T-TL is an unpaid board member of the European Meningococcal and Haemophilus Disease Society and the German Society for Hygiene and Microbiology, committee for microbial systematics, population genetics and infection epidemiology. SM participated on an unpaid advisory board for Pfizer for the meningococcal type B vaccine in South Africa in 2020. WM received funding from GlaxoSmithKline and Pfizer for investigator-initiated research on meningitis B (MenB) strain vaccine coverage. CS received financial support for flights, accommodation, and registration to attend the 2022 ISPPD meeting in Canada. H-CS received funding from Pfizer for a pneumococcal carriage project. H-CS received funding for participation on a data safety monitoring board or advisory board for MSD. LS received personal support from the European Centre for Disease Prevention and Control for attending the European Scientific Conference on Applied Infectious Disease Epidemiology in 2022. MPGvdL received consulting fees from Pfizer, Merck, and GlaxoSmithKline; payment or honoraria from Pfizer and Merck; and support for attending meetings or travel, or both, from Pfizer. AvG is the chairperson for the National Advisory Group on Immunization of South Africa. NMvS received fees for services and consulting fees from MSD and GlaxoSmithKline, and research funding from the Dutch Health Counsel, US National Institutes of Health, and Amsterdam University Medical Centers, and from MSD and GlaxoSmithKline, which are all directly paid to the institution. NMvS holds a patent (WO 2013/020090 A3) on vaccine development against Streptococcus pyogenes. NMvS is an unpaid scientific adviser to the ItsME foundation, and a scientific adviser to the StrepAotearoa New Zealand project but fees are paid to the University of Amsterdam. NMvS holds personal stocks in Genmab. JY received payments for lectures given at scientific meetings organised by MSD and Pfizer; received support from MSD and Pfizer to attend national and international scientific meetings; and participated in advisory boards for MSD and Pfizer. DS is supported by an Oxford Clarendon Scholarship. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)