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This review provides an integrative framework for understanding flaxseed (Linum utassitissimum) as an antimicrobial alternative for poultry production. We begin by familiarizing the reader with the global legislation of antibiotics in animal husbandry; highlighting gaps and current issues for Salmonella enterica (S. enterica) and Eimeria (coccidiosis-inducing). We then discuss the natural, symbiotic characteristics of the Galliformes order (chicken-like birds) and Linum (the flaxes). The key immunological themes in this review include: (i) flaxseed’s regulation of innate and adaptive immunity in chickens, (ii) flaxseed’s ability to accelerate chicken recovery from infection with S. enterica and Eimeria, and (iii) flaxseed’s strengthening of immunity via vitamin B6 antagonism. Research indicates that whole flaxseed increases adaptive immune capacity by augmenting cecal Bacteroides and short-chain fatty acids while also attenuating the heterophil to lymphocyte ratio in chickens. Moreover, flaxseed accelerates chicken recovery from infection with Salmonella Enteritidis or Eimeria tenella; however, future work is needed to better understand (i) defatted flaxseed’s superior performance against Eimeria species and (ii) Eimeria maxima’s resilience against whole flaxseed. In the context of vitamin B6 antagonism, we propose that 15% whole flaxseed overcomes S. enterica’s insult to estrogen synthesis by sustaining the activity of phosphatidylethanolamine methyltransferase (PEMT) in liver. We also propose that 10% defatted flaxseed (as a metformin homologue) strengthens chicken immunity by safeguarding gonadal physiology and by increasing plasma thymidine bioavailability. The concepts in this review can be used as a template for conducting advanced immunological studies in poultry science.

Objectives This case study reports the real-world practicalities of implementing a mixed-methods heat acclimation (HA) programme before the 2022 FIFA World Cup.Methods One male English soccer referee (age: 44 years; height: 1.82 m; body mass: 76.0 kg) who had officiated professionally for over 17 years and had over 10 years’ experience officiating in European and international matches undertook an 11-session HA programme over 22 days. On days 1 and 22, a 30 min fixed-intensity heat tolerance test (9 km.h-1, 2% gradient, 40°C, 40% relative humidity) was performed, and physiological and perceptual responses were measured. A mixed-methods HA approach was used, including environmental chamber isothermic training, post-temperate training saunas and hot water immersion.Results Compared with the pre-test, peak core temperature reduced by 0.40°C (38.4 vs 38.0°C; minimal detectable change (MDC) = 0.34°C), peak skin temperature reduced by 0.5°C (36.7 vs 36.2°C; MDC=0.28°C) and peak heart rate reduced by 5 b·min-1 (167 vs. 162 b·min-1; MDC=4 b·min-1) in the post-test. In the post-test, the sweat rate increased by 17% (1.94 vs 2.27 L.h-1; MDC=0.42 L.h-1). Peak thermal sensation (7 = ‘hot’) and the rating of perceived exertion (3 = ‘moderate’) were unchanged between the tests. However, peak thermal comfort (3 = ‘slightly uncomfortable’ vs 2 = ‘uncomfortable’) was rated lower in the post-test.Conclusion The HA programme elicited positive physiological but indifferent perceptual responses, highlighting that mixed-methods HA can be implemented when a referee still has officiating, travel and training responsibilities during the HA window.

Objectives To investigate the physiological and perceptual responses to wearing a dryrobe for rewarming after passive cold-water immersion (CWI).Methods 15 unhabituated healthy Caucasian men (age: 28.9 (5.4) years) attended the laboratory on three occasions and performed passive CWI (14°C) for 30 min followed by 15 min of rewarming wearing either a dryrobe, towel or foil blanket while positioned in front of fans replicating a 10 mph wind. Physiological (deep body temperature, skin temperature and heart rate) and perceptual (thermal sensation and thermal comfort) variables were measured.Results At 15 min post-immersion, deep body temperature was higher in the dryrobe condition (mean: 37.09 (SD: 0.49)°C) compared with the foil blanket (36.98 (0.64)°C) and towel (36.99 (0.49)°C) (p

Summary: Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Summary: Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs) and myelination (MAMs) respectively, in human patients with multiple sclerosis by integrating public snRNA-seq data. Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in pro-inflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation. In addition, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition toward PEMs. Rosiglitazone could promote microglial phenotype conversion from PEMs to MAMs, thus favoring myelin repair. Taken together, these findings provide insights into therapeutic interventions targeting immunometabolism to switch microglial phenotypes and facilitate regenerative capacity in demyelination.

Abstract Revascularization and angiogenesis, as substrates of sustained collateral circulation, play a crucial role in determining the severity and clinical outcome of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Developing an adjunct biomarker to help identify and monitor collateral status would aid stroke diagnosis and prognosis. To screen the potential biomarkers, proteomic analysis was performed in this study to identify those distinct plasma protein profiles in AIS due to LVO with different collateral status. Interestingly, we found that levels of Plasma Factor VII Activating Protease (FSAP) significantly increased in those AIS patients with poor collaterals, and were correlated with worse neurological outcome. Furtherly, both in vitro and in vivo models of ischemic stroke were used to explore pathological mechanisms of FSAP in endothelial dysfunction. We demonstrated that the FSAP inhibitor, high-molecular-weight hyaluronan (HMW-HA), enhanced the pro-angiogenic vascular factors, improved the integrity of brain blood barrier, and promoted newly formed cerebral microvessels in the ischemic penumbra, consequently improving neurological function. To elucidate the pathways that might contribute to revascularization during LVO, we applied transcriptomic analysis via unbiased RNA sequencing and showed that Wnt signaling was highly involved in FSAP mediated endothelial dysfunction. Notably, inhibition of Wnt5a largely reversed the protective effects from HMW-HA treatment, implying that FSAP might aggravate endothelial dysfunction and neurological deficits by regulating Wnt5a signaling. Therefore, FSAP may represent a potential biomarker for collateral status after LVO and a promising therapeutic target to be explored in the treatment of stroke.

Introduction: Joint preserving surgery for flatfoot reconstruction utilizes correction of bony malalignment and medial soft tissue reconstruction. A medial displacement calcaneal osteotomy (MDCO) can be an essential adjunct to deformity correction and good patient outcomes. Our cadaveric study compares three different surgical techniques utilizing two cannulated screws to best maintain medial translation of the calcaneal osteotomies. Materials and methods: Fifteen above knee fresh-frozen, matched pair cadaveric specimens (30 limbs) were randomized equally to three groups. MDCO were performed on all specimens, followed by manual 10 mm translation. The groups consisted of a “simultaneous drilling,” “staggered drilling,” and a control group, which involved simultaneous drilling of only the near cortex. Following screw fixation, the calcaneal tuberosity was manually translated in a lateral direction. The loss of correction was measured in millimeters. Results: The “simultaneous” drilling group experienced the greatest mean loss of correction at 2.6 mm (range 1.37–3.48 mm). The “staggered” group showed an average loss of 1.16 mm (range 0.36–2.67 mm). The control group demonstrated the greatest maintenance of correction with a mean loss of 0.036 mm (range 0.01–0.06 mm). Conclusions: MDCO realigns the hindfoot adding support to the medial soft tissue reconstruction during flatfoot correction. Loss of initial correction may result in residual deformity and poor long-term outcomes. Our study demonstrates that simultaneous drilling of only the tuberosity near cortex prior to screw fixation was the best at maintaining osteotomy correction. Level of evidence: : Level V, Cadaveric study

Following infection of bacterial cells, bacteriophage modulate double-stranded DNA break repair pathways to protect themselves from host immunity systems and prioritise their own recombinases. Here, we present biochemical and structural analysis of two phage proteins, gp5.9 and Abc2, which target the DNA break resection complex RecBCD. These exemplify two contrasting mechanisms for control of DNA break repair in which the RecBCD complex is either inhibited or co-opted for the benefit of the invading phage. Gp5.9 completely inhibits RecBCD by preventing it from binding to DNA. The RecBCD-gp5.9 structure shows that gp5.9 acts by substrate mimicry, binding predominantly to the RecB arm domain and competing sterically for the DNA binding site. Gp5.9 adopts a parallel coiled-coil architecture that is unprecedented for a natural DNA mimic protein. In contrast, binding of Abc2 does not substantially affect the biochemical activities of isolated RecBCD. The RecBCD-Abc2 structure shows that Abc2 binds to the Chi-recognition domains of the RecC subunit in a position that might enable it to mediate the loading of phage recombinases onto its single-stranded DNA products.

This article illustrates how dietary flaxseed can be used to reduce cancer risk, specifically by attenuating obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). We utilize a targeted metabolomics dataset in combination with a reanalysis of past work to investigate the “metabo-bioenergetic” adaptations that occur in White Leghorn laying hens while consuming dietary flaxseed. Recently, we revealed how the anti-vitamin B6 effects of flaxseed augment one-carbon metabolism in a manner that accelerates S-adenosylmethionine (SAM) biosynthesis. Researchers recently showed that accelerated SAM biosynthesis activates the cell’s master energy sensor, AMP-activated protein kinase (AMPK). Our paper provides evidence that flaxseed upregulates mitochondrial fatty acid oxidation and glycolysis in liver, concomitant with the attenuation of lipogenesis and polyamine biosynthesis. Defatted flaxseed likely functions as a metformin homologue by upregulating hepatic glucose uptake and pyruvate flux through the pyruvate dehydrogenase complex (PDC) in laying hens. In contrast, whole flaxseed appears to attenuate liver steatosis and body mass by modifying mitochondrial fatty acid oxidation and lipogenesis. Several acylcarnitine moieties indicate Randle cycle adaptations that protect mitochondria from metabolic overload when hens consume flaxseed. We also discuss a paradoxical finding whereby flaxseed induces the highest glycated hemoglobin percentage (HbA1c%) ever recorded in birds, and we suspect that hyperglycemia is not the cause. In conclusion, flaxseed modifies bioenergetic pathways to attenuate the risk of obesity, type 2 diabetes, and NAFLD, possibly downstream of SAM biosynthesis. These findings, if reproducible in humans, can be used to lower cancer risk within the general population.

Abstract Background and purpose Neuromyelitis optica spectrum disorder (NMOSD) is mainly an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. Systemic and local inflammatory responses play a key role in the pathophysiology of NMOSD. However, the role of the crucial immunomodulators CD4+CD25+ forkhead box P3+ (Foxp3) regulatory T cells (Tregs) has not been investigated in NMOSD. Methods Twenty-five patients with anti-AQP4-postive NMOSD undergoing an attack and 21 healthy controls (HCs) were enrolled. Frequencies of T cell subsets and Tregs in the peripheral blood were assessed by flow cytometry. Additionally, a model of NMOSD using purified immunoglobulin G from anti-AQP4-antibodies-positive patients with NMOSD and human complement injected into brain of female adult C57BL/6J mice was established. Infiltrated Tregs into NMOSD mouse brain lesions were analyzed by flow cytometry, histological sections, and real-time quantitative Polymerase Chain Reaction. Astrocyte loss, demyelination, and inflammatory response were also evaluated in our NMOSD mouse model. Finally, we examined the effects of both depletion and adoptive transfer of Tregs. Results The percentage of Tregs, especially naïve Tregs, among total T cells in peripheral blood was significantly decreased in NMOSD patients at acute stage when compared to HCs. Within our animal model, the number and proportion of Tregs among CD4+ T cells were increased in the lesion of mice with NMOSD. Depletion of Tregs profoundly enhanced astrocyte loss and demyelination in these mice, while adoptive transfer of Tregs attenuated brain damage. Mechanistically, the absence of Tregs induced more macrophage infiltration, microglial activation, and T cells invasion, and modulated macrophages/microglia toward a classical activation phenotype, releasing more chemokines and pro-inflammatory cytokines. In contrast, Tregs transfer ameliorated immune cell infiltration in NMOSD mice, including macrophages, neutrophils, and T cells, and skewed macrophages and microglia towards an alternative activation phenotype, thereby decreasing the level of chemokines and pro-inflammatory cytokines. Conclusion Tregs may be key immunomodulators ameliorating brain damage via dampening inflammatory response after NMOSD.

Abstract Background Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. Objective This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (ROS) production after lysophosphatidylcholine (LPC)-mediated demyelination. We also explored autophagy in this process. Methods A model of demyelination using two-point LPC injection into the corpus callosum was established. LFB staining, immunofluorescence, Western blot, and electron microscopy were used to study the severity of demyelination. Microglial phenotype and autophagy were detected by immunofluorescence and Western blot. Morris water maze was used to test spatial learning and memory ability. Results We have identified that LPC-mediated myelin damage was reduced by Hv1 deficiency. Furthermore, we found that ROS and autophagy of microglia increased in the demyelination region, which was also inhibited by Hv1 knockout. Conclusion These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation.

Jan Gunnar Dale, 1 Alexander Lüthi, 2 Beate Fundingsland Skaraas, 3 Trude Rundereim, 4 Bjørg Dale 5 1University of Agder, Institute of Health and Nursing Science, Grimstad NO-4898, Norway; 2Lovisenberg Diaconal Hospital, Postoperative Unit, Oslo NO-0440, Norway; 3Municipality of Hå, Health and Social Services, Nærbø NO-4365, Norway; 4Municipality of Kinn, Måløy NO-6701, Norway; 5Centre for Care Research, Southern Norway, University of Agder, Grimstad NO-4898, NorwayCorrespondence: Jan Gunnar DaleUniversity of Agder, Institute of Health and Nursing Science, Post Box 509, Grimstad NO-4898, NorwayTel +47 37 23 37 31Email jan.g.dale@uia.noBackground and Aim: In order to assess patients’ ability to search, understand, and benefit from Internet-based information, several screening tools have been developed. One of these tools, which has been widely used, is the eHealth Literacy Scale (eHEALS). The aim of this study was to examine the measurement properties of the Norwegian version of the eHEALS, as it was used in a group of patients undergoing day surgery.Methods: A cross-sectional survey study was conducted among 119 patients scheduled for day surgical treatment in a Norwegian hospital. The questionnaire included the screening tool eHEALS, which contains 8 items for assessing a person’s information awareness skills, information seeking skills, and skills to evaluate and act based on the information. Cronbach’s alpha coefficients and item-total correlations were assessed for estimating reliability of the eHEALS. Exploratory factor analysis with Oblimin rotation was used for assessing the validity of the scale. Eigenvalue was set to 1.0.Results: A Cronbach’s alpha coefficient of 0.89 for the total scale, values > 0.82 for Alpha if Item Deleted, and moderate to high item-total correlations supported the homogeneity and internal consistency of the scale. A two-component solution explained a total of 74.8% of the variance, with the first component explaining 59.53% of the variance in the scale and included the items reflecting information awareness and seeking. The second component explained 15.23% of the variance, including items reflecting the ability to evaluate and act.Conclusion: The reliability of the Norwegian version of eHEALS, used in a group of patients undergoing day surgery, was good. The internal structure, with two distinct factors, is in line with several previous studies. The eHEALS appears to be an appropriate tool for assessing eHealth literacy among this patient group.Keywords: factor structure, health literacy, internet, internal consistency, screening tool

Else Mari Ruberg Ekra,1 Bjørg Dale2 1Institute of Health and Nursing Science, University of Agder, Grimstad NO-4898, Norway; 2Centre of Caring Research – Southern Norway, Faculty of Health and Sport Sciences, University of Agder, Grimstad NO-4898, NorwayCorrespondence: Else Mari Ruberg Ekra Email else.m.ekra@uia.noBackground and Aim: Using song and music in a systematic way in residential dementia care may have several positive impacts on the patients, as well as the care providers. The aim of this study was to explore how health care providers experienced taking responsibility for conducting a song and music program in dementia care in nursing homes.Methods: An explorative, qualitative study design was used. Focus groups were formed by 17 health care providers from 3 different nursing homes. These providers had experience implementing and using the “Gjenklang” (“reverberation”) song and music program especially developed for people with dementia. Focus group interviews were transcribed verbatim, and systematic text condensation was used for analysing the data.Results: Three categories with associated subcategories emerged from the analysis process. The categories were 1) the music program increased the staff’s consciousness and awareness; 2) the music program evoked the patients’ emotions and reactions; and 3) maintaining enthusiasm over time.Conclusion: The general opinion among the participants was that using the song and music program in a systematic and planned way had many benefits and positive impacts on the patients, as well as the staff. However, it was challenging to make it a part of the daily routine. Thus, it is important that the leaders of the units take responsibility to ensure continuity and maintain engagement among the staff over time.Keywords: dementia, music therapy, music program, qualitative, focus group interviews, nursing homes

Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention., Introduction Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system (CNS) with secondary myelin loss. It disproportionately affects women and non-White populations, typically presents as optic [...]