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Abstract The mucociliary clearance (MC) system is a vital host defense against infection in the lung. MC system function is dependent on ciliary density, structure, and function and airway surface liquid (ASL) composition and hydration. Animal and human studies indicate that MC rate decreases with age which may contribute to the increased rates of pulmonary infection experienced by older people. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes an anion channel on epithelial surfaces that plays a key role in maintaining ASL hydration. Failure or dysfunction of CFTR could result in the dehydration of airway mucus, depressing MC. Here we use two available databases including bulk (GTEx) and single-cell (CELLxGENE) sequencing data from the lung to determine if CFTR expression decreases with age. Bulk expression data and single-cell expression data from goblet, club, and respiratory basal cells all demonstrated patterns of decreasing CFTR expression with age. Ciliated airway cells did not. Secretory cells (including club and goblet cells) and basal cells are the largest source of CFTR expression in the airway. This indicates that changes in CFTR expression and ASL dehydration may contribute to the decreasing MC associated with aging.

Abstract Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.

Abstract Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8–12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9–11, P

The embryonic extracellular matrix (ECM) undergoes transition to mature ECM as development progresses, yet few mechanisms ensuring ECM proteostasis during this period are known. Fibrillin microfibrils are macromolecular ECM complexes serving structural and regulatory roles. In mice, Fbn1 and Fbn2, encoding the major microfibrillar components, are strongly expressed during embryogenesis, but fibrillin-1 is the major component observed in adult tissue microfibrils. Here, analysis of Adamts6 and Adamts10 mutant mouse embryos, lacking these homologous secreted metalloproteases individually and in combination, along with in vitro analysis of microfibrils, measurement of ADAMTS6-fibrillin affinities and N-terminomics discovery of ADAMTS6-cleaved sites, identifies a proteostatic mechanism contributing to postnatal fibrillin-2 reduction and fibrillin-1 dominance. The lack of ADAMTS6, alone and in combination with ADAMTS10 led to excess fibrillin-2 in perichondrium, with impaired skeletal development defined by a drastic reduction of aggrecan and cartilage link protein, impaired BMP signaling in cartilage, and increased GDF5 sequestration in fibrillin-2-rich tissue. Although ADAMTS6 cleaves fibrillin-1 and fibrillin-2 as well as fibronectin, which provides the initial scaffold for microfibril assembly, primacy of the protease-substrate relationship between ADAMTS6 and fibrillin-2 was unequivocally established by reversal of the defects in Adamts6-/- embryos by genetic reduction of Fbn2, but not Fbn1.

Background/AimsInfectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.MethodsWe investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis.ResultsSingle nucleotide polymorphisms in Mannosidase-1-α-2 (MAN1A2) were significantly associated with BA and with other polymorphisms known to affect MAN1A2 expression but were not differentially enriched in either BA subtype. In zebrafish embryos, man1a2 knockdown caused poor biliary network formation, ciliary dysgenesis in Kupffer’s vesicle, cardiac and liver heterotaxy, and dysregulated egfra and other developmental genes. Suboptimal man1a2 knockdown synergized with suboptimal EGFR signaling or suboptimal knockdown of the EGFR pathway gene, adenosine-ribosylation-factor-6, which had minimal effects individually, to reproduce biliary defects but not heterotaxy. In cultured mouse airway epithelium, Man1a2 knockdown arrested ciliary development and motility. Man1a2–/– mice, which experience respiratory failure, also demonstrated portal and bile ductular inflammation. Human BA liver and Man1a2–/– liver exhibited reduced Man1a2 expression and dysregulated ciliary genes, known to cause multisystem human laterality defects.ConclusionBA requiring transplantation associates with sequence variants in MAN1A2. man1a2 regulates laterality, in addition to hepatobiliary morphogenesis, by regulating ciliogenesis in zebrafish and mice, providing a novel developmental basis for multisystem defects in BA.

Knockout mice deficient in the gap junction gene connexin43 exhibit developmental anomalies associated with abnormal neural crest, primordial germ cell, and proepicardial cell migration. These migration defects are due to a loss of directional cell movement, and are associated with abnormal actin stress fiber organization and a loss of polarized cell morphology. To elucidate the mechanism by which Cx43 regulates cell polarity, we used a wound closure assays with mouse embryonic fibroblasts (MEFs) to examine polarized cell morphology and directional cell movement. Studies using embryonic fibroblasts from Cx43 knockout (Cx43KO) mice showed Cx43 deficiency caused cell polarity defects as characterized by a failure of the Golgi apparatus and the microtubule organizing center to reorient with the direction of wound closure. Actin stress fibers at the wound edge also failed to appropriately align, and stabilized microtubule (Glu-tubulin) levels were markedly reduced. Forced expression of Cx43 with deletion of its tubulin-binding domain (Cx43dT) in both wildtype MEFs and neural crest cell explants recapitulated the cell migration defects seen in Cx43KO cells. However, forced expression of Cx43 with point mutation causing gap junction channel closure had no effect on cell motility. TIRF imaging revealed increased microtubule instability in Cx43KO cells, and microtubule targeting of membrane localized Cx43 was reduced with expression of Cx43dT construct in wildtype cells. Together, these findings suggest the essential role of Cx43 gap junctions in development is mediated by regulation of the tubulin cytoskeleton and cell polarity by Cx43 via a nonchannel function.

A economia circular (EC) propõe um modelo de desenvolvimento que favorece o crescimento econômico aliado ao uso racional dos recursos naturais e reaproveitamento dos resíduos. Para mitigar a insegurança alimentar e as emissões de gases, os princípios da EC podem ser aplicados aos sistemas alimentares urbanos. Este estudo aborda como os stakeholders podem influenciar o desenvolvimento da economia circular na constituição de sistemas alimentares urbanos mais sustentáveis e equitativos. A pesquisa analisou dados qualitativos coletados com equipes gestoras das cidades de Rio Branco (AC), Santarém (PA), Recife (PE), Maricá (RJ) e Curitiba (PR) para analisar a governança municipal e identificar boas práticas alinhadas ao desenvolvimento de políticas e programas de fomento a sistemas alimentares circulares. Os resultados sugerem que a mudança para sistemas alimentares circulares requer qualificação das equipes técnicas locais, gestão da qualidade, visão sistêmica da alimentação e governança multinível, além da capacidade de conectar programas de segurança alimentar e nutricional com o intuito de minimizar a geração de resíduos e maximizar o aproveitamento dos alimentos saudáveis. A pesquisa contribui para o avanço da governança dos sistemas alimentares urbanos e fornece insumos para o aprimoramento de políticas públicas locais alinhadas à sustentabilidade ambiental e à soberania alimentar nas cidades.

Objectives: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. Methods: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. Results: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non–COVID-19 septic patients yielded similar results in cell populations and outcome. Conclusions: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Venezuela’s diverse land ecosystems are grouped into four major regions (coast-islands, low plains, hills and mountains), ranging from sea level up to 4978 m. The Scarabaeinae (Scarabaeidae, Coleoptera) currently encompass 278 genera and 6837 species worldwide, but are poorly inventoried in Venezuela. We reviewed the literature and the material housed at the entomological collection of the Universidade Federal de Mato Grosso (CEMT), Cuiabá, Brazil, and found 32 genera and 149 species of dung beetles as certainly present in Venezuela. Twenty-four of these species are, as far as current knowledge goes, endemic to the country, while another 34 are restricted to Venezuela and the neighbouring countries of Colombia, Brazil, Trinidad and Tobago, and Guyana. Additionally, 36 species are deemed potential inhabitants of the country, whilst 14 others previously recorded in the literature as part of the Venezuelan fauna are here concluded not to be actually present there. Complete literature is listed for each genus and species, and information on type material, material examined, worldwide distribution, and Venezuelan records is also presented.

Ossiculoplasty (OPL) aims to restore ossicular chain continuity to improve hearing in patients with conductive or mixed hearing loss, often performed during tympanoplasty. The current training methods, including cadaveric temporal bone models, face challenges such as limited availability, high costs, and biological risks, prompting the exploration of alternative models. This study introduces a novel training platform for OPL using 3D-printed temporal bones and incudes, including a magnified (3:1) model to enhance skill acquisition. Sixty medical students were divided into two groups: one trained on magnified models before transitioning to real-sized ones, and the other used only real-sized models. Training performance was quantitatively assessed using post-remodeling cone-beam CT imaging and mesh distance analysis. The results showed a significant improvement in performance for students with preliminary training on magnified models (87% acceptable results vs. 37%, p = 0.001). Qualitative feedback indicated higher confidence and skill ratings in the magnified model group. This study highlights the effectiveness of scalable, anatomically accurate synthetic models for complex surgical training. While further validation is required with experienced trainees and broader scenarios, the findings support the integration of 3D printing technologies into otologic education, offering a cost-effective, reproducible, and innovative approach to enhancing surgical preparedness.

IntroductionIn recent years, prices for veterinary care have received considerable attention in mainstream media, yet scientific literature has not delved into actual figures. This study aims to elucidate veterinary care costs for dogs, cats, and horses across five countries [Sweden (SE), Norway (NO), Denmark (DK), United Kingdom (UK), and Ireland (IR, with limited data)] through web searches.MethodsUtilising online business directories, we located URLs featuring veterinary care prices in autumn 2022, and repeated tri-monthly five times. Vetpris.se (VP), a price comparison site for SE, NO, and DK, emerged from the search. Additionally, we sought to compare price data from veterinary clinics (ranging from animal hospitals to small private clinics) using a similar approach to VP. We targeted elective procedures (e.g., gonadectomy, GDY) and common procedures (e.g., pyometra surgery in dogs).ResultsComparing data from the same clinics’ websites and from VP within extraction from autumn 2022 to winter 2023/2024, median prices for dog and cat GDY were largely consistent. By October 2023, median prices for male cat GDY ranged from €72 (SE) to €230 (DK), and €130 (SE) to €361 (DK) for females; for dog GDY from €390 (SE) to €599 (DK) for males, and €461 (UK) to €1015 (DK) for females. Across sources, median prices for cat and dog GDY increased by 2–24% over a year for procedures with at least 10 clinics per extraction. Equine GDY (per sedation and local analgaesia) in SE saw a 64% increase by year-end, with a median price of €492. Emergency surgeries during regular-hours (e.g., pyometra and caesarean section) in SE were approximately €2,300 at the last extraction, marking a 27% increase for pyometra surgery during regular-hours and 15% after-hours compared to the previous year. Variability existed within and across countries and diagnoses/procedures.DiscussionCross-validation suggested VP generally provided reliable information, though data points for emergencies were limited. Our web searching tool necessitated extensive manual verification, indicating room for further development. We recommend enhancing price transparency for animal owners to become better informed about the cost of veterinary care and be able to make informed choices.

Background Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood.Methods An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected.Results 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity.Conclusions in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Abstract Objective To explore Chat Generative Pretrained Transformer's (ChatGPT's) capability to create multiple‐choice questions about otorhinolaryngology (ORL). Study Design Experimental question generation and exam simulation. Setting Tertiary academic center. Methods ChatGPT 3.5 was prompted: “Can you please create a challenging 20‐question multiple‐choice questionnaire about clinical cases in otolaryngology, offering five answer options?.” The generated questionnaire was sent to medical students, residents, and consultants. Questions were investigated regarding quality criteria. Answers were anonymized and the resulting data was analyzed in terms of difficulty and internal consistency. Results ChatGPT 3.5 generated 20 exam questions of which 1 question was considered off‐topic, 3 questions had a false answer, and 3 questions had multiple correct answers. Subspecialty theme repartition was as follows: 5 questions were on otology, 5 about rhinology, and 10 questions addressed head and neck. The qualities of focus and relevance were good while the vignette and distractor qualities were low. The level of difficulty was suitable for undergraduate medical students (n = 24), but too easy for residents (n = 30) or consultants (n = 10) in ORL. Cronbach's α was highest (.69) with 15 selected questions using students' results. Conclusion ChatGPT 3.5 is able to generate grammatically correct simple ORL multiple choice questions for a medical student level. However, the overall quality of the questions was average, needing thorough review and revision by a medical expert to ensure suitability in future exams.

Abstract Whereas aging is a whole-organism process, senescence is a cell mechanism that can be triggered by several stimuli. There is increasing evidence that critical conditions activate cell senescence programs irrespective of patient’s age. In this review, we briefly describe the basic senescence pathways and the consequences of their activation in critically ill patients. The available evidence suggests a paradigm in which activation of senescence can be beneficial in the short term by rendering cells resistant to apoptosis, but also detrimental in a late phase by inducing a pro-inflammatory and pro-fibrotic state. Senescence can be a therapeutic target. The use of drugs that eliminate senescent cells (senolytics) or the senescence-associated phenotype (senomorphics) will require monitoring of these cell responses and identification of therapeutic windows to improve the outcome of critically ill patients.

Abstract Variations in the Toll‐interacting protein (TOLLIP) gene have been identified in genome‐wide association studies to correlate with risk of disease, mortality, and response to N‐acetylcysteine therapy in idiopathic pulmonary fibrosis. Although TOLLIP is known to modulate innate immune responses, its relevance in organ fibrogenesis remains unknown. Prior work in the literature suggests TOLLIP dampens transforming growth factor beta (TGFβ) signaling in human cell lines. In this study, we examined the role of TOLLIP in mouse lung fibroblast (MLF) responses to TGFβ and in the bleomycin model of experimental lung fibrosis using Tollip−/− mice. We hypothesize that if TOLLIP negatively regulates TGFβ signaling, then Tollip−/− mouse lung fibroblasts (MLFs) would have enhanced response to TGFβ treatment, and Tollip−/− mice would develop increased fibrosis following bleomycin challenge. Primary MLFs were stimulated with TGFβ (1 ng/mL) for 24 h. RNA was obtained to assess global transcriptional responses by RNA‐seq and markers of myofibroblast transition by qPCR. Functional assessment of TGFβ‐stimulated MLFs included cell migration by scratch assay, cell proliferation, and matrix invasion through Matrigel. In the in vivo model of lung fibrosis, Tollip−/− mice and wild‐type (WT) littermates were administered bleomycin intratracheally and assessed for fibrosis. We further examined TGFβ signaling in vivo after bleomycin injury by SMAD2, ERK1/2, and TGFβR1 Western blot. In response to TGFβ treatment, both WT and Tollip−/− MLFs exhibited global transcriptional changes consistent with myofibroblast differentiation. However, Tollip−/− MLFs showed greater number of differentially expressed genes compared to WT MLFs and greater upregulation of Acta2 by qPCR. Functionally, Tollip−/− MLFs also exhibited increased migration and Matrigel invasiveness compared to WT. We found evidence of enhanced TGFβ signaling in Tollip−/− through SMAD2 in vitro and in vivo. Tollip−/− mice experienced lower survival using a standard weight‐adjusted dosing without evidence of differences in fibrosis at Day 21. With adjustment of dosing for sex, no differences were observed in fibrosis at Day 21. However, Tollip−/− mice had greater weight loss and increased bronchoalveolar lavage fluid total protein during early resolution at Day 14 compared to WT without evidence of differences in acute lung injury at Day 7, suggesting impaired resolution of lung injury.

In the Greek regions of Agrafa and Tzoumerka, Tsalafouti, a traditional spreadable cheese made from goat’s and sheep’s milk is produced. This product has emerged in recent years as a result of the campaign to acquire Geographical Indication. This study aimed to assess the biopeptide profile of Tsalafouti cheese in order to highlight its nutritional value. Using HPLC-MS, bioactive peptides in Tsalafouti cheese samples were identified and classified according to their bioactivity. The biopeptides detected are known to present antibacterial, anti-diabetic, anti-hypertensive, anti-thrombotic, antioxidant, and immunomodulatory activities, while ACE enzyme and dipeptidyl-4 (DPP-IV) inhibitors were also identified. Based on these results, Tsalafouti cheese presents an interesting bioactive peptides profile that may act as special motivation for consumers to choose this specific cheese.

Abstract Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative rare disease characterized by symptoms and signs in the upper and lower motor neurons, leading to progressive neuro-degeneration and muscle atrophy. Our objective was to analyse the quality of life (QoL) in patients with ALS and compare with general population and with patients with cancer. Prospective study from consecutive ALS patients in one center. In order to assess quality of life, during the first visit three questionnaires were administered: Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Short Form-36 (SF-36) and EuroQoL 5D (EQ-5D). We compared SF-36 of ALS patients with a reference population (n = 9151), and we compared the EQ-5D index score of ALS patients versus patients with cancer in the same area and in the same period (2015–2018). Between June 2015 and September 2017, 23 were included. The mean age was 65.1 ± 12.6 years and 56.5% were women. Compared with the general population, patients with ALS showed lowest QoL (p

Abstract Excitability and contraction of cardiac muscle from brain‐dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+‐handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain‐dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole‐cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L‐type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain‐dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.

Abstract Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor‐dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor‐dependent gene expression suggests new potential genes involved in cell–cell interactions beyond what ligand‐receptor co‐expression can discover.

Abstract Characterization of tissue architecture promises to deliver insights into development, cell communication, and disease. In silico spatial domain retrieval methods have been developed for spatial transcriptomics (ST) data assuming transcriptional similarity of neighboring barcodes. However, domain retrieval approaches with this assumption cannot work in complex tissues composed of multiple cell types. This task becomes especially challenging in cellular resolution ST methods. We developed Vesalius to decipher tissue anatomy from ST data by applying image processing technology. Vesalius uniquely detected territories composed of multiple cell types and successfully recovered tissue structures in high‐resolution ST data including in mouse brain, embryo, liver, and colon. Utilizing this tissue architecture, Vesalius identified tissue morphology‐specific gene expression and regional specific gene expression changes for astrocytes, interneuron, oligodendrocytes, and entorhinal cells in the mouse brain.

Abstract This study analyzed the frequency and intensity of acute stress among health professionals caring for COVID-19 patients in four Latin American Spanish-speaking countries during the outbreak. A cross-sectional study involved a non-probability sample of healthcare professionals in four Latin American countries. Participants from each country were invited using a platform and mobile application designed for this study. Hospital and primary care workers from different services caring for COVID-19 patients were included. The EASE Scale (SARS-CoV-2 Emotional Overload Scale, in Spanish named Escala Auto-aplicada de Sobrecarga Emocional) was a previously validated measure of acute stress. EASE scores were described overall by age, sex, work area, and experience of being ill with COVID-19. Using the Mann–Whitney U test, the EASE scores were compared according to the most critical moments of the pandemic. Univariate and multivariate analysis was performed to investigate associations between these factors and the outcome ‘acute stress’. Finally, the Kruskal–Wallis was used to compare EASE scores and the experience of being ill. A total of 1372 professionals responded to all the items in the EASE scale: 375 (27.3%) Argentines, 365 (26.6%) Colombians, 345 (25.1%) Chileans, 209 (15.2%) Ecuadorians, and 78 (5.7%) from other countries. 27% of providers suffered middle-higher acute stress due to the outbreak. Worse results were observed in moments of peak incidence of cases (14.3 ± 5.3 vs. 6.9 ± 1.7, p

Se registran nuevas localidades para la especie Oxysternon ebeninum (Nevison, 1890) al norte del estado Amazonas, Venezuela, donde las condiciones ambientales de estos lugares son significativamente diferentes a las reportadas previamente en la literatura.

Background: Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR

Background Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.Methods We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.Results The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum–neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.Conclusion The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.

Resumen: En neonatología, al igual que en otras especialidades, hay indicaciones y prácticas que son aplicadas sin tener evidencia científica. En este artículo se analizan algunas de ellas con la metodología “Critical Appraisal Topic” (CAT), se presenta la evidencia encontrada y la conclusión basada en esta evidencia.Resultados de la búsqueda: - El baño del recién nacido se puede efectuar a partir de las 24 horas de vida sin riesgo y con beneficios asociados. - Es preferible el aseo en seco del cordón umbilical que con antisépticos en países con buenos índices de salud y baja tasa de onfalitis. - La caída tardía del cordón umbilical, por sí solo y sin estar asociado a otras infecciones, no se relaciona a inmunodeficiencias. - No se encuentra evidencia que contraindique la salida habitual fuera del hogar durante el periodo neonatal. - El papiloma preauricular aislado no se asocia a malformaciones del sistema nefrourinario. - No hay evidencia científica acerca de la cantidad de abrigo óptimo del neonato y lactante, encontrándose sólo recomendaciones de experto. Sin embargo, existe evidencia sobre asociación entre muerte súbita y temperatura ambiental. Conclusión: A partir de estos resultados, se demuestra que deben cuestionarse estas creencias y muchas otras prácticas clínicas habituales. Debe buscarse evidencia científica para hacer recomendaciones que faciliten el cuidado de los pacientes y eviten daño, además de no caer en prácticas que implican mayores costos. Summary: In neonatology, as in other specialties, there are indications and clinical practices that are applied without having solid scientific evidence. In this article, we analyzed common clinical practices with Critical Appraisal Topic (CAT) methodology. Our conclusions are based on the following evidence:Search results: - Newborn's first bath can be carried out after 24 hours of life without risk and with associated benefits. - Dry cleansing of the umbilical cord is preferable to antiseptics in countries with good health indices and a low rate of omphalitis. - Delayed umbilical cord drop, by itself and not associated with other infections, is not related with immunodeficiencies. - No evidence of contraindications for taking newborns outside their homes during their neonatal period was found. - Isolated preauricular papilloma is not associated with nephrourinary system malformations. - There is no scientific evidence about the optimal amount of neonatal and infant clothing, only expert recommendations. However, there is evidence of an association between environmental temperature and sudden infant death. Conclusions: Based on these results, we presented proof that these common clinical practices, and many others, should be questioned. Scientific evidence should be seeked in order to make better recommendations for patients that will aid them in their care and with their child, and concurrently avoid harm and higher costs.

The study of the interaction between the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor is key to understanding binding affinity and stability. In the present report, we sought to investigate the differences between two already sequenced genome variants (Spanish and British) of SARS-CoV-2. Methods: In silico model evaluating the homology, identity and similarity in the genome sequence and the structure and alignment of the predictive spike by computational docking methods. Results: The identity results between the Spanish and British variants of the Spike protein were 28.67%. This close correspondence in the results between the Spanish and British SARS-CoV-2 variants shows that they are very similar (99.99%). The alignment obtained results in four deletions. There were 23 nucleotide substitutions also predicted which could affect the functionality of the proteins produced from this sequence. The interaction between the binding receptor domain from the spike protein and the ACE2 receptor produces some of the mutations found and, therefore, the energy of this ligand varies. However, the estimated antigenicity of the British variant is higher than its Spanish counterpart. Conclusions: Our results indicate that minimal mutations could interfere in the infectivity of the virus due to changes in the fitness between host cell recognition and interaction proteins. In particular, the N501Y substitution, situated in the RBD of the spike of the British variant, might be the reason for its extraordinary infective potential.

BackgroundThe fundamentals of the infectivity and immune evasion of the SARS-CoV-2 Omicron variant are not yet fully understood. Here, we carried out an in-silico study analyzing the spike protein, the protein electrostatic potential, and the potential immune evasion.MethodsThe analysis was based on the structure of the spike protein from two SARS-CoV-2 variants, the original Wuhan and the Botswana (Omicron). The full-length genome sequences and protein sequences were obtained from databanks. The interaction of the spike proteins with the human Angiotensin Converting Enzyme 2 (ACE2) receptor was evaluated through the open-source software. The Immune Epitope Database was used to analyze the potential immune evasion of the viruses.ResultsOur data show that the Omicron spike protein resulted in 37 amino acid changes. The physicochemical properties of the spike had changed, and the electrostatic potentials differed between both variants. This resulted in a decrease in protein interactions, which does not establish a greater interaction with the ACE2 receptor. These changes compromise key receptor-binding motif residues in the SARS-CoV-2 spike protein that interact with neutralizing antibodies and ACE2.ConclusionsThese mutations appear to confer enhanced properties of infectivity. The Omicron variant appears to be more effective at evading immune responses.

Abstract Background Cardiogenic pulmonary oedema (CPE) may contribute to ventilator-associated lung injury (VALI) in patients with cardiogenic shock. The appropriate ventilatory strategy remains unclear. We aimed to evaluate the impact of ultra-low tidal volume ventilation with tidal volume of 3 ml/kg predicted body weight (PBW) in patients with CPE and veno–arterial extracorporeal membrane oxygenation (V–A ECMO) on lung inflammation compared to conventional ventilation. Methods A single-centre randomized crossover trial was performed in the Cardiac Intensive Care Unit (ICU) at a tertiary university hospital. Seventeen adults requiring V–A ECMO and mechanical ventilation due to cardiogenic shock were included from February 2017 to December 2018. Patients were ventilated for two consecutive periods of 24 h with tidal volumes of 6 and 3 ml/kg of PBW, respectively, applied in random order. Primary outcome was the change in proinflammatory mediators in bronchoalveolar lavage fluid (BALF) between both ventilatory strategies. Results Ventilation with 3 ml/kg PBW yielded lower driving pressures and end-expiratory lung volumes. Overall, there were no differences in BALF cytokines. Post hoc analyses revealed that patients with high baseline levels of IL-6 showed statistically significant lower levels of IL-6 and IL-8 during ultra-low tidal volume ventilation. This reduction was significantly proportional to the decrease in driving pressure. In contrast, those with lower IL-6 baseline levels showed a significant increase in these biomarkers. Conclusions Ultra-low tidal volume ventilation in patients with CPE and V–A ECMO may attenuate inflammation in selected cases. VALI may be driven by an interaction between the individual proinflammatory profile and the mechanical load overimposed by the ventilator. Trial registration The trial was registered in ClinicalTrials.gov (identifier NCT03041428, Registration date: 2nd February 2017).

This article presents results on the Spanish phraseologically bound words (PLF), also known as cranberry words, based on a corpus analysis. If up to now the different Spanish PLF had been collected introspectively, this article presents a list of the Spanish PLF indicating the phraseological fixation index (IFF) of each one of them in the phraseological unit (UF) that contains them and ordered by the weighted phraseological fixation index (IFFP). To do this, it has been necessary to obtain from the corpus the total number of occurrences of the PLF (NPLF) and to analyse the fixation of these elements both inside the UF or the UFS that contain them (FFPLF) and outside the UF, in their free use. Furthermore, the quantitative data of the PLF which was collected in four differentiated groups from two matrices (the FFPLF matrix and the NPLF matrix) present interesting results on this type of elements.

BackgroundAortic valve replacement is the gold standard treatment for severe symptomatic aortic stenosis, but thrombosis of bioprosthetic valves (PVT) remains a concern.ObjectiveTo analyze the factors involved in the contact pathway during aortic valve replacement and to assess their impact on the development of thromboembolic complications.MethodsThe study was conducted in 232 consecutive patients who underwent: transcatheter aortic valve replacement (TAVR, N = 155), and surgical valve replacement (SAVR, N = 77) (MUVITAVI project). Demographic and clinical data, outcomes including a combined end point (CEP) of thrombotic events, and imaging controls were recruited. Samples were collected 24 h before and 48 h after valve replacement. FXII, FXI and (pre)kallikrein were evaluated by Western Blot and specific ELISA with nanobodies.ResultsThe CEP of thrombotic events was reached by 19 patients: 13 patients presented systemic embolic events and 6 patients subclinical PVT. Valve replacement did not cause FXII activation or generation of kallikrein. There was a significant reduction of FXI levels associated with the procedure, which was statistically more pronounced in SAVR than in TAVR. Cases with reductions of FXI below 80% of basal values had a lower incidence of embolic events during the procedure than patients in whom FXI increased above 150%: 2.7 vs. 16.7%; p: 0.04.ConclusionTAVR or SAVR did not significantly activate the contact pathway. A significant reduction of FXI, was observed, particularly in SAVR, associated with lower incidence of thrombotic events. These results encourage evaluating the usefulness and safety of FXI-directed antithrombotic treatments in these patients.

Abstract Background Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality. Methods Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis. Results Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP)

Los patrones de agrupación presentes en un conjunto urbano de pequeña escala en la costa norte de Colombia son el objeto de estudio. Al iniciar las observaciones, la vivienda local mostró las particularidades constructivas generadas por la necesidad de edificarla sobre el agua. Este atributo especial dentro de las arquitecturas vernáculas en Colombia señaló una condición por desarrollar. Analizar el contexto de estas arquitecturas y enmarcar las configuraciones del conjunto fueron las dos partes del desarrollo de la investigación. Con los resultados se contrastaron las características del conjunto y los patrones o los atributos que describen las lógicas de este proceso particular, se desarrolló una metodología para abordar cómo combinar dos aspectos: por una parte, las lógicas constructivas usadas para las viviendas de la zona (los materiales, los sistemas y las lógicas constructivas); por otra, cómo pasan a otra lógica: una de agrupación o de conjunto. En este último aspecto, las morfologías y las tipologías particulares son algo por referenciar con detalle en Colombia, en marco de lo vernáculo o las arquitecturas rurales.

Entrevista de Cecília Loreto Mariz a Alberto da Silva Moreira sobre a pessoa e a obra de Peter Berger.

Objective To analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical trial, from the public health system perspective.Design An economic evaluation was conducted for the within-trial period (2 years) comparing the four arms of the INDICA study.Setting Primary care in the Canary Islands, Spain.Participants 2334 patients with T2DM without complications were included.Interventions Interventions for patients (PTI), for primary care professionals (PFI), for both (combined intervention arm for patients and professionals, CBI) and usual care (UC) as a control group.Outcomes The main outcome was the incremental cost per quality-adjusted life-years (QALY). Only the intervention and the healthcare costs were included.Analysis Multilevel models were used to estimate results, and to measure the size and significance of incremental changes. Missed values were treated by means of multiple imputations procedure.Results There were no differences between arms in terms of costs (p=0.093), while some differences were observed in terms of QALYs after 2 years of follow-up (p=0.028). PFI and CBI arms were dominated by the other two arms, PTI and UC. The differences between the PTI and the UC arms were very small in terms of QALYs, but significant in terms of healthcare costs (p=0.045). The total cost of the PTI arm (€2571, 95% CI €2317 to €2826) was lower than the cost in the UC arm (€2750, 95% CI €2506 to €2995), but this difference did not reach statistical significance. Base case estimates of the incremental cost per QALY indicate that the PTI strategy was the cost-effective option.Conclusions The INDICA intervention designed for patients with T2DM and families is likely to be cost-effective from the public healthcare perspective. A cost-effectiveness model should explore this in the long term.Trial registration number NCT01657227.

People living with HIV (PLH) experience higher rates of HPV infection as well as an increased risk of HPV-related disease, including malignancies. Although they are considered a high-priority group for HPV vaccination, there are limited data regarding the long-term immunogenicity and efficacy of HPV vaccines in this population. Seroconversion rates and geometric mean titers elicited by vaccination are lower in PLH compared to immunocompetent participants, especially in individuals with CD4 counts below 200 cells/mm3 and a detectable viral load. The significance of these differences is still unclear, as a correlate of protection has not been identified. Few studies have focused on demonstrating vaccine efficacy in PLH, with variable results depending on the age at vaccination and baseline seropositivity. Although waning humoral immunity for HPV seems to be more rapid in this population, there is evidence that suggests that seropositivity lasts at least 2–4 years following vaccination. Further research is needed to determine the differences between vaccine formulations and the impact of administrating additional doses on durability of immune protection.

Background The impact of quarantine in older adults have been reported in several studies with contradictory results, reporting from negative effects to no significant outcomes or even beneficial consequences. Heterogeneity in aging plays a role in each region, the aim of this study is to analyze the impact of quarantine on health conditions (physical and mental) and lifestyle in older adults in five Centro American countries during COVID-19 pandemic. Method In this cross-sectional study, n = 712 older adults 60 years and older from Mexico, Guatemala, El Salvador, Honduras and Costa Rica were assessed by telephone. Sociodemographic data, physical and mental health, lifestyle and quarantine conditions were asked previous informed consent. Results In general, mean of days in quarantine at the moment of the study was 142 days (approximately four months and three weeks). In the analysis of the impact of the days in quarantine effects were found on the frequency of falls, functional ability in Activities of Daily Living (ADL), general cognitive function, memory, orientation, language, frequency of drinking alcohol, having a balanced diet, and being active cognitively. Some differences were found between countries. Conclusions Effects of quarantine on older adults in Centro America, requires attention of governments and healthcare to prevent long term morbidity and disability, and to promote healthy aging.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29–4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01–4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

The sustainability of dairying has been questioned, yet cattle exploit non-food resources (especially forages) and provide key nutrients for consumers’ health. This study, using different forage types, considered milk’s nutritional quality, focusing on fatty acid profiles alongside methane emissions—investigating whether methane can be predicted from milk fatty acids (FAs). Compared with grass/clover/maize silage, cows grazing grass/clover pasture produced milk 70% higher in beneficial omega-3 FAs, which increased by an additional 15% when grazing more diverse pasture. Milk from grazing also had less omega-6 FAs (compared with silage diets), and their ratio with omega-3 FAs fell from 2.5:1 on silage to 1.2:1 when grazing grass/clover and 1.1:1 on diverse pasture. Measured methane emissions (at 8.7 g/kg energy-corrected milk) were lower than published values, and existing models for estimating methane from lactating cows were poor predictors for this dataset. The multiple regression of methane against milk FAs in this study provided predictions with an R2 of 0.56 for daily emissions and 0.65 relative to milk output. Grazing quality and a diverse pasture with productive cows were potentially beneficial to milk nutritional quality, and our results reinforce the theory that milk fat composition could be an accessible tool for methane prediction; however, they also suggest that more work is needed for alternative production systems.

Objective This study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients’ (T2DM) reported outcomes measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions.Participants A total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres.Setting Primary Care Centers in Canary Islands (Spain).Intervention The intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients’ results. A third group received both PTI and PFI (combined intervention, CBI).Outcome measure Cognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables.Results Compared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p

I shall study in this paper prayers and magic spells that circulates today as an important part of popular culture studies. These prayers and spells especially said to harm someone appear under various different forms which connect ancient times to current times, becoming part of lyra minima tradition. RESUMEN: Las oraciones y conjuros mágicos que actualmente aún circulan ofrecen material para estudiar los como una rama de la literatura popular. Estas oraciones y conjuros para hacer daño a alguien tienen distintas versiones y variantes que conectan a la antigüedad con la actualidad, formando parte de la tradición.

Abstract This is the first case of a patient taking aprepitant for a post‐acute COVID‐19 syndrome. This case may encourage researchers to look for the evidence for the efficacy and safety of a neurokinin 1 receptor antagonist in this frequent syndrome.

The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes within FLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory at FLC and encapsulates generic mechanisms that may be widely applicable.

The challenges of implementing interventions in healthcare settings have been more apparent during the COVID-19 pandemic. This pre-implementation evaluation used a rapid qualitative approach to explore barriers and facilitators to an intervention in intensive care units in Argentina, aimed to promote the use of personal protection equipment, provide emotional support for professionals, and achieve patient flow goals. Data were collected using semi-structured interviews with health professionals of 15 public hospitals in Argentina. Normalization Process Theory was used to guide content analysis of the data. Participants identified potential barriers such as the incorporation of non-specialist staff, shortage of resources, lack of communication between groups and shifts. Potential facilitators were also identified: regular feedback and communication related to implementation, adequate training for new and non-specialist staff, and incentives (e.g., scholarships). The immediacy of the pandemic demanded rapid qualitative research, sharing actionable findings in real time.

Intensive confinement (IC) systems for dairying have become widespread during the last decades. However, potential advantages of alternative systems such as full-grazing (FG) or integrated dairy/cash-crop (IFG) systems with regards to better provision of ecosystem services are widely discussed. To investigate performance and environmental impacts, we compared four prevailing dairy systems using an on-farm research study. The farm types differed in their share of pasture access and quantity of resource inputs: (i) an IC with a high import of supplements and mineral fertilizers; (ii) a semi-confinement (SC) with daytime pasture access during summer and moderate import of supplementary feeds representing the base-line scenario; (iii) a FG based on grazed seeded grass-clover swards with no purchased N-fertilizers and low quantities of supplementary feeds; and (iv) an IFG comparable to FG but based on grass-clover leys integrated in a cash-crop rotation. Results revealed highest milk productivity (16 t energy-corrected-milk (ECM) ha−1) and farm-N-balance (230 kg N ha−1) in IC; however, the highest product carbon footprint (PCF; 1.2 CO2eq kg ECM−1) and highest N-footprint (13 g N kg ECM−1) were found in the baseline system SC. The FG and IFG revealed on average similar forage dry matter yields (10 – 11 t DM ha−1) at similar crude protein and net-energy-lactation ratios per kg DM-intake compared to the IC and SC. The PCF in FG were comparable to IC (0.9 vs. 1.1 kg CO2eq kg ECM−1) but at a lower N-footprint (9 vs. 12 g N kg ECM−1). However, despite low measured N-losses in the FG system, the farm-N-surplus was exceeded by 90 kg N ha−1. A further reduction was only possible in the IFG (50 kg N ha−1) by accounting for a potential N-carry-over from N-rich plant residues to the cash-crop unit, leading to the lowest PCF (0.6 kg CO2eq kg ECM−1) for the IFG, with still moderate milk yield levels (~10,500 kg ECM ha−1). According to this bottom-up approach based on field data, improved integrated grazing systems could provide an important opportunity to increase the ecosystem services from dairy farming, operating with land use efficiencies similar to IC.

Intussuscepção é o prolapso de um segmento intestinal no lúmen da alça intestinal adjacente. Embora frequentemente idiopático, um dos fatores predisponentes inclui parasitismo intestinal. O objetivo deste relato foi descrever o caso incomum de intussuscepção ileo-ileal em um gato filhote co-parasitado por Cystoisospora felis e Giardia intestinalis. Um gato, de três meses de idade, sem raça definida, foi atendido com episódios de vômitos intermitentes, prostração, emagrecimento progressivo, desconforto abdominal e diarreia com dois dias de duração. A presença de numerosos cistos de G. intestinalis. e oocistos de C. felis foram detectados nas fezes. O protocolo terapêutico não obteve resposta desejada, o paciente evoluiu para um quadro de choque hipovolêmico e foi à óbito. Durante o atendimento emergencial, foi possível detectar uma massa abdominal palpável de formato cilíndrico na região caudal do abdômen. Na necropsia, foi observado um quadro de ileítefibrino purulenta e necrosante secundária a intussuscepção. O hiperperistaltismo intestinal associado ao intenso parasitismo por esses protozoários sugere a participação desses parasitos na gênese da afecção. O diagnóstico precoce dessas parasitoses é de suma importância tanto para melhorar a qualidade de vida do paciente, quanto para obter um bom prognóstico nesses casos de intussuscepção decorrente de distúrbios intestinais provocados pelo parasitismo.