Acute Challenge Research Articles

Combined In Vivo Microdialysis and PET Studies to Validate [11C]Yohimbine Binding as a Marker of Noradrenaline Release.

The noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [11C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device. Microdialysis probes were placed in the thalamus, striatum and cortex and dialysis samples were collected every 10 min. Three 90 min [11C]yohimbine scans were acquired: at baseline and at two timepoints after the administration of amphetamine (1-10 mg/kg), a non-specific releaser of dopamine and noradrenaline, or nisoxetine (1 mg/kg), a specific noradrenaline transporter inhibitor. [11C]yohimbine volumes of distribution (VT) were obtained using the Logan kinetic model. Both challenges induced a significant decrease in yohimbine VT, with time courses reflecting their different mechanisms of action. Dialysis samples revealed a significant increase in noradrenaline extracellular concentrations after challenge and an inverse correlation with changes in yohimbine VT. These data suggest that [11C]yohimbine can be used to evaluate acute variations in synaptic noradrenaline concentrations after pharmacological challenges.

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice.

Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users

The acute cardiovascular and pulmonary effects of contemporary electronic nicotine delivery systems (ENDS) in long-term users are not known. What are the cardiovascular and pulmonary responses to an acute 15-min product use challenge with ENDS and combustible cigarettes in regular nicotine-containing product users compared with control participants who do not use tobacco or vape? Observational challenge study before and after nicotine-containing product use of 395 individuals who used ENDS exclusively (n= 164; exhaled carbon monoxide level,< 5 parts per million [ppm]; positive urine NicCheck I [Mossman Associates] results, 82%; fourth-generation ENDS), participants who smoked cigarettes exclusively (n= 117; carbon monoxide level, > 5 ppm; positive urine NicCheck I results), and control participants (n= 114; carbon monoxide level,< 5 ppm; negative urine NicCheck I results). During the 15-min product challenge, cigarette users took a median of 14.0 puffs (interquartile range [IQR], 9.3 puffs); ENDS users took 9.0 puffs (IQR, 7.5 puffs; P< .001). After product challenge, compared with control participants, ENDS users showed greater increases in adjusted mean differences in systolic BP (5.6mmHg [95%CI, 4.4-6.8mmHg] vs2.3mmHg [95%CI, 0.8-3.8mmHg]; P= .001), diastolic BP (4.2mmHg [95%CI, 3.3-5.0mmHg] vs2.0mmHg [95%CI, 1.1-3.0mmHg; P= .003), and heart rate (4.8 beats/min [95%CI, 4.0-5.6 beats/min] vs-1.3 beats/min [95%CI, -2.2 to -0.3 beats/min]; P< .001) and greater reductions in brachial artery diameter (-0.011cm [95%CI, -0.013 to 0.009cm] vs-0.006cm [95%CI, -0.004 to -0.009cm]; P= .003), time-domain heart rate variability (-7.2 ms [95%CI, -10.5 to -3.7 ms] vs3.6 ms [95%CI, 1.6-9.3 ms]; P= .001), and FEV1 (ENDS: -4.1 [95%CI, -5.4 to -2.8] vscontrol participants: -1.1 [95%CI, -2.7 to 0.6]; P= .005) with values similar to those of cigarette users. ENDS users performed worse than control participants on all exercise parameters, notably metabolic equivalents (METs; adjusted mean difference, 1.28 METs [95%CI, 0.73-1.83 METs]; P< .001) and 60-s heart rate recovery (adjusted mean difference, 2.9 beats/min [95%CI, 0.7-5.0 beats/min]; P= .008). ENDS users had acute worsening of blood pressure, heart rate, and heart rate variability, as well as vasoconstriction, impaired exercise tolerance, and increased airflow obstruction after vaping, compared to control participants. ClinicalTrials.gov; No.: NCT03863509; URL: www. gov.

Nutrition and health implications of preterm children born to adolescent mothers

Preterm birth is one of the most important determinants of adverse infant outcomes, in terms of survival and quality of life. Adolescent pregnant is among the factors that are associated with an increased risk of preterm birth. However, despite its significant contribution, this age group has not received sufficient attention in efforts to prevent and reduce the burden of preterm births. The current efforts are generalized to all age groups and do not consider that adolescents have special age requirements even before becoming pregnant. This literature review summarizes some of the key nutrition and health challenges in pregnant adolescent that are linked to preterm birth as well as possible acute and chronic nutritional and health challenges to their preterm children. Electronic databases such as PubMed, Google Scholar, and MEDLINE were searched using keywords such as “adolescent”, “health,” “preterm”, “Teen mothers”, “nutrition” “preterm birth” and pertinent articles (N&nbsp;= 74) were retrieved and reviewed. Due to maternal young age, preterm children of adolescent mothers also have high risk of suffering from short and long adverse health and nutritional problems. Female adolescents should not only be viewed from one angle of growing girls but also as part of women of the reproductive age group. They should not receive any less of the benefits of this age group that include adequate education about reproductive health, pregnancy nutrition and use and choice of contraceptives.

114 Stay Interviews: Guiding Meaningful Conversations for Retention of High-Quality CRPs

OBJECTIVES/GOALS: Clinical Research Professional (CRP) shortages and high turnover rates directly impact the conduct of studies. A strategy for improving CRP retention is using Stay Interviews (SI), which are intentional exchanges between CRPs and leadership to enhance transparency and trust. Importantly, SIs are entirely separate from performance evaluations. METHODS/STUDY POPULATION: Representatives from seven academic medical centers formed a collaborative workgroup (WG) as part of the Association for Clinical and Translational Science (ACTS) Clinical Research Professionals Taskforce (CRPT) Special Interest Group (SIG). The purpose of this workgroup was to develop a Stay Interview (SI) toolkit that will empower leadership to retain high quality staff by engaging employees in open and responsive conversations about motivations to stay in their current roles. Tools previously used by collaborating institutions were evaluated and aligned to establish a sharable guide for SI best practices. Training resources to support leaders in effectively using SI tools were also developed to accompany the toolkit. RESULTS/ANTICIPATED RESULTS: Discussions of current tool use among group members highlighted 2 categorical use cases: continuous integration to promote workforce engagement and retention; and targeted use to address acute workforce challenges. The WG identified the need for a standardized conversation guide as well as leadership tools to support effective use of the guide. From the examples collated, the group crafted a 14 question SI guide with additional probing questions that can be tailored to the work environment. Questions fell into 4 key themes: likes/dislikes, motivations, workplace influence on work life, and professional development barriers and opportunities. Anecdotally, SI use in other industries suggests that wide adoption is likely to reduce CRP workforce turnover and improve job satisfaction. DISCUSSION/SIGNIFICANCE: SIs are designed to build trust and strengthen relationships, fostering positive change by acknowledging issues, understanding motivations, and increasing engagement. Leaders can make immediate actions: clearing obstacles, providing new resources, and increasing recognition. Our next step is implementing a pilot to gather workforce metrics.

A Psychodynamic Approach to Co-occurring Borderline Personality and Substance Use Disorders in the Emergency Department.

Patients with co-occurring substance use disorders and borderline personality disorder have high rates of morbidity, mortality, and utilization of medical services. Their acute symptoms present complex challenges to clinical staff in the medical emergency department related to both logistics and management of countertransference. This article examines patterns in countertransference and proposes application of psychodynamically informed principles and strategies to facilitate safety and enhance communication during fraught clinical encounters.

Cold temperatures induce priming of the glucose stress response in tree swallows

Capricious environments often present wild animals with challenges that coincide or occur in sequence. Conceptual models of the stress response predict that one threat may prime or dampen the response to another. Although evidence has supported this for glucocorticoid responses, much less is known about the effects of previous challenges on energy mobilization. Food limitation may have a particularly important effect, by altering the ability to mobilize energy when faced with a subsequent challenge. We tested the prediction that challenging weather conditions, which reduce food availability, alter the energetic response to a subsequent acute challenge (capture and restraint). Using a three-year dataset from female tree swallows measured during three substages of breeding, we used a model comparison approach to test if weather (temperature, wind speed, and precipitation) over 3- or 72-hour timescales predicted baseline and post-restraint glucose levels, and if so which environmental factors were the strongest predictors. Contrary to our predictions, weather conditions did not affect baseline glucose; however, birds that had experienced lower temperatures over the preceding 72 h tended to have higher stress-induced glucose when faced with an acute stressor. We also saw some support for an effect of rainfall on stress-induced glucose: around the time that eggs hatched, birds that had experienced more rainfall over the preceding 72 h mounted lower responses. Overall, we find support in a wild animal for the idea that the glucose stress response may be primed by exposure to prior challenges.

Transient inhibition of meniscus cell migration following acute inflammatory challenge.

Meniscus tears represent a common orthopedic injury that often requires surgery to restore pain-free function. The need for surgical intervention is due, in part, to the inflammatory and catabolic environment that inhibits meniscus healing after injury. In other organ systems, healing is dependent on the migration of cells to the site of injury; however, in the meniscus, it is currently unknown how the microenvironment dictates cell migration in the postinjury inflamed setting. Here, we investigated how inflammatory cytokines alter meniscal fibrochondrocyte (MFC) migration and sensation of microenvironmental stiffness. We further tested whether an FDA approved interleukin-1 receptor antagonist (IL-1Ra; Anakinra) could rescue migratory deficits caused by inflammatory challenge. When cultured in the presence of inflammatory cytokines (tumor necrosis factor-α [TNF-α] or interleukin-1β [IL-1β]) for 1 day, MFC migration was inhibited for 3 days before returning to control levels at Day 7. This migratory deficit was clear in three-dimensional as well, where fewer MFCs exposed to inflammatory cytokines migrated from a living meniscal explant compared with control. Notably, addition of IL-1Ra to MFCs previously exposed to IL-1β restored migration to baseline levels. This study demonstrates that joint inflammation can have negative impacts on meniscus cell migration and mechanosensation, affecting their potential for repair, and that resolution of this inflammation with concurrent anti-inflammatories can reverse these deficits. Future work will apply these findings to mitigate the negative consequences of joint inflammation and promote repair in a clinically relevant meniscus injury model.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

Comprehensive transcriptional and metabolomic analysis reveals the neuroprotective mechanism of dietary gamma-aminobutyric acid response to hypoxic stress in the Chinese mitten crab (Eriocheir sinensis)

Hypoxia is one of the serious stress challenges that aquatic animals face throughout their life. Our previous study found that hypoxia stress could induce neural excitotoxicity and neuronal apoptosis in Eriocheir sinensis, and observed that gamma-aminobutyric acid (GABA) has a positive neuroprotective effect on juvenile crabs under hypoxia. To reveal the neuroprotective pathway and metabolic regulatory mechanism of GABA in E. sinensis exposed to hypoxia stress, an 8-week feeding trial and acute hypoxia challenge were performed. Subsequently, we performed a comprehensive transcriptomic and metabolomic analysis of the thoracic ganglia of juvenile crabs. Differential genes and differential metabolites were co-annotated to 11 KEGG pathways, and further significant analysis showed that only the sphingolipid signaling pathway and the arachidonic acid metabolism pathway were significantly enriched. In the sphingolipid signaling pathway, GABA treatment significantly increased long-chain ceramide content in thoracic ganglia, which exerted neuroprotective effects by activating downstream signals to inhibit hypoxia-induced apoptosis. Moreover, in the arachidonic acid metabolism pathway, GABA could increase the content of neuroprotective active substances and reduce the content of harmful metabolites by regulating the metabolism of arachidonic acid for inflammatory regulation and neuroprotection. Furthermore, the decrease of glucose and lactate levels in the hemolymph suggests the positive role of GABA in metabolic regulation. This study reveals the neuroprotective pathways and possible mechanisms of GABA in juvenile E. sinensis exposed to hypoxia stress and inspires the discovery of new targets for improving hypoxia tolerance in aquatic animals.

‘Being able to work has kept our life fairly constant:’ reconciling social practice models to assess the impact of (infra)structural inequities on household wellbeing during the COVID-19 pandemic

Social practice theory offers a multidisciplinary perspective on the relationship between infrastructure and wellbeing. One prominent model in practice theory frames systems of provision as the rules, resources, and structures that enable the organization of social practices, encompassing both material and immaterial aspects of infrastructures. A second well-known model frames social practices in terms of their constituent elements: meanings, materials, and competences. Reconciling these two models, we argue that household capacity to respond to shifting systems of provision to maintain wellbeing is profoundly tied to the dynamics of privilege and inequity. To examine these dynamics, we propose a new analytical tool utilizing the Bourdieuian conceptualization of forms of capital, deepening the ability of social practice theory to address structural inequities by re-examining the question of who is able to access specific infrastructures. To illustrate this approach, we examine how households adapted to shifting systems of provision during the COVID-19 pandemic. Using data from 183 households in the Midwestern United States, we apply this tool to analyze adaptations to disruptions of multiple systems of provision, including work, school, food, and health, from February 2020 to August 2021. We highlight how household wellbeing during the pandemic has been impacted by forms of capital available to specific households, even as new social practices surrounding COVID-19 prevention became increasingly politicized. This research provides insight into both acute challenges and resilient social practices involving household consumption, indicating a need for policies that can address structural inequities across multiple systems of provision.

Dairy Cows Offered Fresh Chicory Instead of Ensiled Pasture during an Acute Heat Challenge Produced More Milk and Had Lower Body Temperatures.

The frequency, duration, and intensity of heat waves in Australia are increasing. To reduce the impact of heat waves on milk production, novel management strategies are required. Altering the forage type and amount offered affect the heat load on dairy cows and offer potential strategies to ameliorate the effects of hot weather. Thirty-two multiparous, lactating Holstein-Friesian cows were assigned one of four dietary treatments: chicory high amount, chicory low amount, pasture silage high amount, or pasture silage low amount. These cows were exposed to a heat wave in controlled-environment chambers. Cows that were offered fresh chicory had similar feed intake to cows that were offered pasture silage (15.3 kg DM/d). However, cows that were offered chicory produced greater energy-corrected milk (21.9 vs. 17.2 kg/d) and had a lower maximum body temperature (39.4 vs. 39.6 °C) than cows that were offered pasture silage overall. Cows that were offered the high amount of forage had greater feed intake (16.5 vs. 14.1 kg DM/d) and energy corrected milk yield (20.0 vs. 17.9 kg/d) than cows that were offered the low amount, as intended, but with no difference in maximum body temperature (39.5 °C). We conclude that feeding chicory instead of pasture silage to dairy cows shows promise as a dietary strategy to ameliorate the effect of heat exposure, and there was no advantage in restricting feed amount.

Defensive walls: A neglected security strategy in northern Nigeria

Nigeria from 2016 to 2023 has been facing new security challenges, including kidnapping of people for ransom, sporadic shooting of inhabitants, and the rustling of livestock. There is a rich history of how cities in Nigeria, erected defensive walls or fortifications to protect the inhabitants and their property against invaders, criminals, or rustlers centuries before the arrival of the European colonialists to Africa. The incessant attacks on rural communities, highways and urban centres have compelled criminologists and security experts to rethink and revisit the security strategies adopted in the past and worked effectively in protecting the populace and their belongings. Kingdoms and Empires, as well as Emirates in different parts of Africa, had developed or erected defensive walls or fortifications which if replicated in the 21st century, will ease neighbhourhood watch and community surveillance and policing. This paper has helped to identify cities in Nigeria with defensive walls and restrict entrances (gates) in places such as Kano, Katsina Sokoto, Zaria and Benin City. These are some of the cities known for prehistoric warfare and their people were brave and famous in intercity and inter-community battles. The study found that towns and cities in Nigeria and other parts of the world used defensive walls or fortified their jurisdiction against enemies or invaders. The strategy proved effective in protecting their people and property. Building defensive walls or fortifications of towns and cities that are facing acute security challenges in Nigeria can enable the Government and community members to protect the residents. The use of defensive walls will make the use of different mass surveillance tactics much easier because the areas are cordoned-off hence patrol, searching and arrest of criminals. Therefore, the researcher recommended that instead of spending huge amounts on the procurement of weapons by the Federal Government of Nigeria, the Government should erect or build fences that make criminal investigation more effective hence combat crime and criminals.

A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration.

Although antipsychotics' mechanisms of action have been thoroughly investigated, they have not been fully elucidated at the network level. We tested the hypothesis that acute pre-treatment with ketamine (KET) and administration of asenapine (ASE) would modulate the functional connectivity of brain areas relevant to the pathophysiology of schizophrenia, based on transcript levels of Homer1a, an immediate early gene encoding a key molecule of the dendritic spine. Sprague-Dawley rats (n = 20) were assigned to KET (30 mg/kg) or vehicle (VEH). Each pre-treatment group (n = 10) was randomly split into two arms, receiving ASE (0.3 mg/kg), or VEH. Homer1a mRNA levels were evaluated by in situ hybridization in 33 regions of interest (ROIs). We computed all possible pairwise Pearson correlations and generated a network for each treatment group. Acute KET challenge was associated with negative correlations between the medial portion of cingulate cortex/indusium griseum and other ROIs, not detectable in other treatment groups. KET/ASE group showed significantly higher inter-correlations between medial cingulate cortex/indusium griseum and lateral putamen, the upper lip of the primary somatosensory cortex, septal area nuclei, and claustrum, in comparison to the KET/VEH network. ASE exposure was associated with changes in subcortical-cortical connectivity and an increase in centrality measures of the cingulate cortex and lateral septal nuclei. In conclusion, ASE was found to finely regulate brain connectivity by modelling the synaptic architecture and restoring a functional pattern of interregional co-activation.

Retinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice

Retinoids are potent transcriptional regulators that act in regulating cell proliferation, differentiation, and other cellular processes. We carried out studies in male mice to establish the importance of local cellular retinoid stores within the lung alveolus for maintaining its health in the face of an acute inflammatory challenge induced by intranasal instillation of lipopolysaccharide. We also undertook single cell RNA sequencing and bioinformatic analyses to identify roles for different alveolar cell populations involved in mediating these retinoid-dependent responses. Here we show that local retinoid stores and uncompromised metabolism and signaling within the lung are required to lessen the severity of an acute inflammatory challenge. Unexpectedly, our data also establish that alveolar cells other than lipofibroblasts, specifically microvascular endothelial and alveolar epithelial cells, are able to take up lipoprotein-transported retinoid and to accumulate cellular retinoid stores that are directly used to respond to an acute inflammatory challenge.

Chitosan-thymolsulfonephthalein-cobalt nanocomposites for colorimetric detection of sulfide anions in aqueous solution

BackgroundWater pollution by sulfide ions, arising from the exploration and exploitation of sulfide mineral ore, can cause many chronic and acute health challenges. However, owing to the cost of sophisticated equipment and technical expertise required to detect anionic sulfides in water has inspired the preparation of easy-to-use naked-eye colorimetric devices. MethodsIn this study, the functionalization of chitosan solution with thymolsulfonephthalein solution (CFTS) at moderate conditions was utilized for the chemical synthesis of cobalt nanocomposites (CFTS-CoNCs) based chemosensors. ResultsThe prepared material's scanning electron micrograph shows the high Co dispersion on the surface of CFTS with a thorn-shaped morphology in uniform spheres. In contrast, the transmission electron micrograph shows good dispersibility of the tiny rod-like particles distributed on a dendrite-like surface. The interaction of the orange-colored CFTS-CoNCs chemosensor solution with the colorless S2− ions was accompanied by an instant and stable black color change. Furthermore, the selective and sensitive chemosensor could detect ≥ 15 ppm aqueous S2− ions solution at lower pH. The mechanism of detection could be due to a nucleophilic attack of S2− on the cobalt-induced hydroxylmethylpropyl benzoxathiole amine cation giving rise to the strong UV–Vis absorption at 592 nm. ConclusionThe highly selective and sensitive CFTS-CoNCs chemosensor can be applied for real-time and quick on-site analysis. In addition, the colorimetric device will serve as a lifesaver in terms of reducing both time and cost, user-friendly, and hands-on tools for the rapid/accurate detection of sulfide ions in water.

Large-scale physically accurate modelling of real proton exchange membrane fuel cell with deep learning

Proton exchange membrane fuel cells, consuming hydrogen and oxygen to generate clean electricity and water, suffer acute liquid water challenges. Accurate liquid water modelling is inherently challenging due to the multi-phase, multi-component, reactive dynamics within multi-scale, multi-layered porous media. In addition, currently inadequate imaging and modelling capabilities are limiting simulations to small areas (<1 mm2) or simplified architectures. Herein, an advancement in water modelling is achieved using X-ray micro-computed tomography, deep learned super-resolution, multi-label segmentation, and direct multi-phase simulation. The resulting image is the most resolved domain (16 mm2 with 700 nm voxel resolution) and the largest direct multi-phase flow simulation of a fuel cell. This generalisable approach unveils multi-scale water clustering and transport mechanisms over large dry and flooded areas in the gas diffusion layer and flow fields, paving the way for next generation proton exchange membrane fuel cells with optimised structures and wettabilities.

Intestinal SEC16B modulates obesity by regulating chylomicron metabolism

ObjectiveGenome-wide association studies (GWAS) have identified genetic variants in SEC16 homolog B (SEC16B) locus to be associated with obesity and body mass index (BMI) in various populations. SEC16B encodes a scaffold protein located at endoplasmic reticulum (ER) exit sites that is implicated to participate in the trafficking of COPII vesicles in mammalian cells. However, the function of SEC16B in vivo, especially in lipid metabolism, has not been investigated. MethodsWe generated Sec16b intestinal knockout (IKO) mice and assessed the impact of its deficiency on high-fat diet (HFD) induced obesity and lipid absorption in both male and female mice. We examined lipid absorption in vivo by acute oil challenge and fasting/HFD refeeding. Biochemical analyses and imaging studies were performed to understand the underlying mechanisms. ResultsOur results showed that Sec16b intestinal knockout (IKO) mice, especially female mice, were protected from HFD-induced obesity. Loss of Sec16b in intestine dramatically reduced postprandial serum triglyceride output upon intragastric lipid load or during overnight fasting and HFD refeeding. Further studies showed that intestinal Sec16b deficiency impaired apoB lipidation and chylomicron secretion. ConclusionsOur studies demonstrated that intestinal SEC16B is required for dietary lipid absorption in mice. These results revealed that SEC16B plays important roles in chylomicron metabolism, which may shed light on the association between variants in SEC16B and obesity in human.

SOLARIA-SensOr-driven resiLient and adaptive monitoRIng of farm Animals

Sensor-enabled big data and artificial intelligence platforms have the potential to address global socio-economic trends related to the livestock production sector through advances in the digitization of precision livestock farming. The increased interest in animal welfare, the likely reduction in the number of animals in relation to population growth in the coming decade and the growing demand for animal proteins pose an acute challenge to prioritizing animal welfare on the one hand, while maximizing the efficiency of production systems on the other. Current digital approaches do not meet these challenges due to a lack of efficient and lack of real-time non-invasive precision measurement technologies that can detect and monitor animal diseases and identify resilience in animals. In this opinion review paper, I offer a critical view of the potential of wearable sensor technologies as a unique and necessary contribution to the global market for farm animal health monitoring. To stimulate the sustainable, digital and resilient recovery of the agricultural and livestock industrial sector, there is an urgent need for testing and developing new ideas and products such as wearable sensors. By validating and demonstrating a fully functional wearable sensor prototype within an operational environment on the livestock farm that includes a miniaturized animal-borne biosensor and an artificial intelligence (AI)-based data acquisition and processing platform, the current needs, which have not yet been met, can be fulfilled. The expected quantifiable results from wearable biosensors will demonstrate that the digitization technology can perform acceptably within the performance parameters specified by the agricultural sector and under operational conditions, to measurably improve livestock productivity and health. The successful implementation of the digital wearable sensor networks would provide actionable real-time information on animal health status and can be deployed directly on the livestock farm, which will strengthen the green and digital recovery of the economy due to its significant and innovative potential.

Feline Uroepithelial Cell Culture as a Novel Model of Idiopathic Cystitis: Investigations on the Effects of Norepinephrine on Inflammatory Response, Oxidative Stress, and Barrier Function.

Feline idiopathic cystitis (FIC) is one of the most common urinary tract disorders in domestic cats. As stress is suggested to play a key role in the pathogenesis of FIC, the effects of norepinephrine (NE) as a stress mediator were investigated on a novel feline primary uroepithelial cell culture, serving as an in vitro model of the disease. The uroepithelial cells gained from the mucosa of the bladder of a euthanized cat were cultured for 6 days and were acutely exposed to NE (10, 100, and 1000 µM) for 1 h. NE increased the metabolic activity of the cultured cells and elevated the extracellular concentrations of the pro-inflammatory mediators interleukin-6 (IL-6) and stromal cell derived factor 1 (SDF-1), confirming that NE can trigger an inflammatory response in the uroepithelium. Cellular protein carbonyl levels were increased by NE exposure, while malondialdehyde and glucose regulated protein 78 concentrations remained unchanged, indicating that NE may provoke the oxidative damage of proteins without inducing lipid peroxidation or endoplasmic reticulum stress. Further, it can be strongly suggested that an acute NE challenge might diminish the barrier function of uroepithelial cells, as reflected by the decreased glycosaminoglycan concentration, claudin-4 protein expression, and reduced TER values of the NE-treated cell cultures. Based on these results, short-term NE exposure mimicking acute stress can provoke an inflammatory response and decrease the barrier integrity of cultured feline uroepithelial cells. Hence, it is highly expected that stress-associated NE release may play an important mediatory role in the pathogenesis of FIC.