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The East African country of Djibouti is known to host an important seasonal feeding aggregation of whale sharks that allows the frequent observation of their surface feeding behaviour. The influence of environmental factors on the different whale shark feeding strategies (passive, active, and vertical) was studied over a four-year period (2017, 2020, 2022, 2024) in the Gulf of Tadjoura. Across 81 immature male whale sharks identified and 1082 surface feeding behaviours recorded in this period, the chlorophyll-a concentration was the main parameter predicting the choice of the filter-feeding technique. Active and vertical feeding behaviours were associated with rainfall, lower sea surface temperature, worse sea conditions, and low wind speed during the morning, all factors positively correlated to chlorophyll-a concentration. On the contrary, passive feeding behaviour was favoured in the inverse environmental conditions. Both passive and vertical feeding behaviours occurred during El Niño events, whereas active feeding was more common during La Niña events. Since it is known that whale shark abundance and distribution are associated with food availability at coastal locations, it is fundamental to understand environmental drivers of filter-feeding strategies when managing conservation efforts for this endangered species. Recommendations for future research work at this site are presented.

Children (N = 103, 4-9 years, 59 females, 84% White, c. 2019) completed visual processing, visual feature integration (color, luminance, motion), and visual search tasks. Contrast sensitivity and feature search improved with age similarly for luminance and color-defined targets. Incidental feature integration improved more with age for color-motion than luminance-motion. Individual differences in feature search ([beta] = 0.11) and incidental feature integration ([beta] = 0.06) mediated age-related changes in conjunction visual search, an index of visual selective attention. These findings suggest that visual selective attention is best conceptualized as a series of developmental trajectories, within an individual, that vary by an object's defining features. These data have implications for design of educational and interventional strategies intended to maximize attention for learning and memory.

Infection by the liver fluke, Fasciola hepatica, places a substantial burden on the global agri-food industry and poses a significant threat to human health in endemic regions. Widespread resistance to a limited arsenal of chemotherapeutics, including the frontline flukicide triclabendazole (TCBZ), renders F. hepatica control unsustainable and accentuates the need for novel therapeutic target discovery. A key facet of F. hepatica biology is a population of specialised stem cells which drive growth and development - their dysregulation is hypothesised to represent an appealing avenue for control. The exploitation of this system as a therapeutic target is impeded by a lack of understanding of the molecular mechanisms underpinning F. hepatica growth and development. Wnt signalling pathways govern a myriad of stem cell processes during embryogenesis and drive tumorigenesis in adult tissues in animals. Here, we identify five putative Wnt ligands and five Frizzled receptors in liver fluke transcriptomic datasets and find that Wnt/β-catenin signalling is most active in juveniles, the most pathogenic life stage. FISH-mediated transcript localisation revealed partitioning of the five Wnt ligands, with each displaying a distinct expression pattern, consistent with each Wnt regulating the development of different cell/tissue types. The silencing of each individual Wnt or Frizzled gene yielded significant reductions in juvenile worm growth and, in select cases, blunted the proliferation of neoblast-like cells. Notably, silencing FhCTNNB1, the key effector of the Wnt/β-catenin signal cascade led to aberrant development of the neuromuscular system which ultimately proved lethal - the first report of a lethal RNAi-induced phenotype in F. hepatica. The absence of any discernible phenotypes following the silencing of the inhibitory Wnt/β-catenin destruction complex components is consistent with low destruction complex activity in rapidly developing juvenile worms, corroborates transcriptomic expression profiles and underscores the importance of Wnt signalling as a key molecular driver of growth and development in early-stage juvenile fluke. The putative pharmacological inhibition of Wnt/β-catenin signalling using commercially available inhibitors phenocopied RNAi results and provides impetus for drug repurposing. Taken together, these data functionally and chemically validate the targeting of Wnt signalling as a novel strategy to undermine the pathogenicity of juvenile F. hepatica.

ObjectivesMaternal occupational exposures during early pregnancy can be detrimental to foetus health and have short- and long-term health effects on the child. This study examined their association with adverse birth outcomes.MethodsThe study included 3938 nulliparous women from the Italian NINFEA mother-child cohort. Their occupational exposures during the first trimester of pregnancy were assessed through prospectively collected questionnaire information and job-exposure matrices. Associations between maternal exposures and birthweight, preterm birth, and delivery by caesarean section were analysed by multivariable linear and logistic regression models. An exploratory factor analysis was carried out to explore co-exposure profiles in association with birth outcomes.ResultsWomen exposed to passive smoking at work and those who reduced their working hours during pregnancy were found to have an increased likelihood of all analysed birth outcomes. Children of mothers performing a demanding work were less likely to be born preterm [OR 0.72 (95% CI 0.54 to 0.95)] and more likely to have a higher birthweight [β = 40.4 g (95% CI 7.5 to 73.4)]. Maternal exposures to heat and dust were associated with a lower birthweight [β = -160.1 g (95% CI -299.6 to -20.7)] and increased odds of caesarean section [OR 6.99 (95% CI 2.36 to 25.47)], respectively.ConclusionsThis study provides some evidence of the selection of healthy population into the workforce and of association between work-related passive smoking, heat and dust and adverse birth outcomes.

Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initially infects the respiratory tract, it also directly or indirectly affects other organs, including the brain. However, little is known about the relative neurotropism of SARS-CoV-2 variants of concern (VOCs), including Omicron (B.1.1.529), which emerged in November 2021 and has remained the dominant pathogenic lineage since then. To address this gap, we examined the relative ability of Omicron, Beta (B.1.351), and Delta (B.1.617.2) to infect the brain in the context of a functional human immune system by using human angiotensin-converting enzyme 2 (hACE2) knock-in triple-immunodeficient NGC mice with or without reconstitution with human CD34+ stem cells. Intranasal inoculation of huCD34+-hACE2-NCG mice with Beta and Delta resulted in productive infection of the nasal cavity, lungs, and brain on day 3 post-infection, but Omicron was surprisingly unique in its failure to infect either the nasal tissue or brain. Moreover, the same infection pattern was observed in hACE2-NCG mice, indicating that antiviral immunity was not responsible for the lack of Omicron neurotropism. In independent experiments, we demonstrate that nasal inoculation with Beta or with D614G, an ancestral SARS-CoV-2 with undetectable replication in huCD34+-hACE2-NCG mice, resulted in a robust response by human innate immune cells, T cells, and B cells, confirming that exposure to SARS-CoV-2, even without detectable infection, is sufficient to induce an antiviral immune response. Collectively, these results suggest that modeling of the neurologic and immunologic sequelae of SARS-CoV-2 infection requires careful selection of the appropriate SARS-CoV-2 strain in the context of a specific mouse model.

Summary: Background: Mouse models that recapitulate key features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are important tools for understanding complex interactions between host genetics, immune responses, and SARS-CoV-2 pathogenesis. Little is known about how predominantly cellular (Th1 type) versus humoral (Th2 type) immune responses influence SARS-CoV-2 dynamics, including infectivity and disease course. Methods: We generated knock-in (KI) mice expressing human ACE2 (hACE2) and/or human TMPRSS2 (hTMPRSS2) on Th1-biased (C57BL/6; B6) and Th2-biased (BALB/c) genetic backgrounds. Mice were infected intranasally with SARS-CoV-2 Delta (B.1.617.2) or Omicron BA.1 (B.1.1.529) variants, followed by assessment of disease course, respiratory tract infection, lung histopathology, and humoral and cellular immune responses. Findings: In both B6 and BALB/c mice, hACE2 expression was required for infection of the lungs with Delta, but not Omicron BA.1. Disease severity was greater in Omicron BA.1-infected hTMPRSS2-KI and double-KI BALB/c mice compared with B6 mice, and in Delta-infected double-KI B6 and BALB/c mice compared with hACE2-KI mice. hACE2-KI B6 mice developed more severe lung pathology and more robust SARS-CoV-2-specific splenic CD8 T cell responses compared with hACE2-KI BALB/c mice. There were no notable differences between the two genetic backgrounds in plasma cell, germinal center B cell, or antibody responses to SARS-CoV-2. Interpretation: SARS-CoV-2 Delta and Omicron BA.1 infection, disease course, and CD8 T cell response are influenced by the host genetic background. These humanized mice hold promise as important tools for investigating the mechanisms underlying the heterogeneity of SARS-CoV-2-induced pathogenesis and immune response. Funding: This work was funded by NIH U19 AI142790-02S1, the GHR Foundation, the Arvin Gottleib Foundation, and the Overton family (to SS and EOS); Prebys Foundation (to SS); NIH R44 AI157900 (to KJ); and by an American Association of Immunologists Career Reentry Fellowship (FASB).

IntroductionFor nearly two centuries, cranberry (Vaccinium macrocarpon Ait.) breeders have improved fruit quality and yield by selecting traits on fruiting stems, termed “reproductive uprights.” Crop improvement is accelerating rapidly in contemporary breeding programs due to modern genetic tools and high-throughput phenotyping methods, improving selection efficiency and accuracy.MethodsWe conducted genotypic evaluation on 29 primary traits encompassing fruit quality, yield, and chemical composition in two full-sib cranberry breeding populations—CNJ02 (n = 168) and CNJ04 (n = 67)—over 3 years. Genetic characterization was further performed on 11 secondary traits derived from these primary traits.ResultsFor CNJ02, 170 major quantitative trait loci (QTL; R2≥ 0.10) were found with interval mapping, 150 major QTL were found with model mapping, and 9 QTL were found to be stable across multiple years. In CNJ04, 69 major QTL were found with interval mapping, 81 major QTL were found with model mapping, and 4 QTL were found to be stable across multiple years. Meta-QTL represent stable genomic regions consistent across multiple years, populations, studies, or traits. Seven multi-trait meta-QTL were found in CNJ02, one in CNJ04, and one in the combined analysis of both populations. A total of 22 meta-QTL were identified in cross-study, cross-population analysis using digital traits for berry shape and size (8 meta-QTL), digital images for berry color (2 meta-QTL), and three-study cross-analysis (12 meta-QTL).DiscussionTogether, these meta-QTL anchor high-throughput fruit quality phenotyping techniques to traditional phenotyping methods, validating state-of-the-art methods in cranberry phenotyping that will improve breeding accuracy, efficiency, and genetic gain in this globally significant fruit crop.

Pseudohypoxic brain swelling, also known as postoperative intracranial hypotension-associated venous congestion, is an intriguing complication following routine neurosurgical interventions. We report a case of a 73-year-old female patient who exhibited this rare complication following an elective L4–L5 laminectomy, without evidence of intraoperative cerebrospinal fluid leakage. Initially presenting with clinical features suggestive of anoxic/hypoxic brain injury, the case deviated from typical pseudohypoxic ischemic venous hypertension (PIHV) patterns, leading to a challenging diagnostic process. The patient's remarkable recovery, contrary to the initial grim prognosis, emphasizes the critical need for considering PIHV in differential diagnoses when postoperative symptoms mimic anoxic/hypoxic brain injuries. This case contributes to the evolving understanding of PIHV, particularly in scenarios lacking conventional risk factors like cerebral spinal fluid (CSF) leakage, and underscores the importance of comprehensive postoperative surveillance and management. It also highlights the imperative for continued research into the pathophysiology and treatment strategies of PIHV to enhance patient outcomes in complex surgical contexts.

IntroductionWhile autonomic failure is a well-known prognostic factor for more aggressive disease progression in Parkinson's disease (PD), with a three- to sevenfold higher risk of dementia and death within 10 years after the diagnosis, the individual impact of cardiovascular, gastrointestinal, urogenital, thermoregulatory, and pupillomotor autonomic domains on PD clinical outcomes remains unclear.ObjectivesWe sought to determine the 5-year risk of developing dementia, falls, postural instability, dysarthria, and dysphagia in PD patients with and without autonomic impairment at baseline and to assess the joint and individual association of each autonomic domain on these key functional outcomes. In addition, we aimed to determine the impact of each autonomic domain on activities of daily living (ADLs) and health-related quality of life (HRQoL).MethodsWe enrolled 65 consecutive PD patients in a 5-year cohort study involving standardized evaluations of autonomic symptoms, orthostatic hypotension, and motor and non-motor features, including cognitive function. Associations were estimated as odds ratio and adjusted for PD duration, age, and baseline motor impairment.ResultsCardiovascular dysautonomia was associated with a sevenfold higher risk of developing dementia (95%CI: 1.154-50.436; p = 0.035) and a fivefold higher risk of falls (95%CI: 1.099-18.949; p = 0.039), as well as significantly higher impairment in ADLs (p = 0.042) and HRQoL (p = 0.031). No relevant associations were found between the other autonomic domains and these outcomes.ConclusionsCardiovascular dysautonomia, but not other domains, showed an association with worse 5-year clinical outcomes in PD. Our data suggest a specific role for cardiovascular autonomic dysregulation in the pathogenic mechanisms of PD progression.

Comme les autres plathelminthes, les Monogènes sont riches en substances neuroactives. En plus des composants neuronaux aminergiques et cholinergiques à action rapide, impliqués dans la régulation des réponses sensorielles chez les vers, existent en grand nombre des éléments peptidergiques à action lente. Ceux-ci interviennent probablement dans la régulation à plus long terme des réactions et des comportements. En utilisant des techniques immunochimiques, on a pu mettre en évidence à ce jour jusqu'à 10 immunoréactions régulatrices peptidiques chez le Monogène Diclidophora merlangi. Parmi ces peptides, le neuropeptide F (NPF) est de loin le plus abondant, ce qui conforte les observations déjà faites chez les représentants des principaux phyllums d'invertébrés étudiés. Chez D. merlangi., le NPF se trouve largement réparti dans les structures nerveuses centrale et périphérique, y compris celles liées à l'appareil reproducteur. De plus, dans l'appareil reproducteur femelle, l'innervation des muscles responsables des séries de contractions-relaxations nécessaires à l'accumulation des oeufs semble être exclusivement peptidergique. Tandis que les propriétés fonctionnelles du NPF doivent être maintenant déterminées, sa localisation intracellulaire au niveau des jonctions neuromusculaires de l'ootype chez D. merlangi étaye l'hypothèse d'une intervention peptidergique dans la fonction reproductive, et plus précisément dans la coordination des séquences présidant à la formation de l'oeuf.

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Introduction: Tight glycemic control is essential for optimal outcomes after coronary artery bypass graft (CABG) surgery, regardless of pre-operative diabetes status. The ideal timing for transitioning from intravenous (IV) to subcutaneous (SC) insulin remains unclear. This study addresses this knowledge gap by comparing the effects of early transition (postoperative day 1, POD1) versus delayed transition on glycemic control and patient outcomes after CABG surgery. Methods: We analyzed data from a single tertiary medical center focusing on patients receiving insulin during their CABG hospitalization between 1 and 31 October 2022. We divided patients into two groups based on their transition timing: (1) Delayed Transition Group, patients transitioned from IV insulin infusion to SC insulin after POD1; and (2) Early Transition Group, patients transitioned on POD1. The primary outcome was the incidence of euglycemia on POD1. Secondary outcomes included rates of maintaining euglycemia from POD1 until POD10 or hospital discharge, hospital length of stay (LOS), ICU LOS, mean glucose levels, rates of hyperglycemia (blood glucose > 180 mg/dL) and hypoglycemia (blood glucose < 70 mg/dL), and rate of restarting IV insulin. Statistical analysis adjusted for BMI and diabetes diagnosis. Results: A total of 394 patients were enrolled, with 68 patients (17.3%) in the delayed-transition group and 326 patients (82.7%) in the early-transition group. Majority of the patients were males (74%), with an average age of 67 ± 9 years. Mean HbA1C and creatinine levels were comparable between the two groups. Patients in the early-transition group experienced a shorter ICU and hospital length of stay compared to the delayed-transition group, without a higher risk of restarting IV insulin. Conclusions: Early transition from IV insulin drip to SC insulin on POD1 of CABG surgery reduces ICU and hospital LOS without increasing the risk of transitioning back to IV insulin.