The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Phosphorus adsorption and organic release from dried and thermally treated water treatment sludge.

The study investigated water treatment sludge (WTS) as a phosphorus (P) adsorbent and examined the release of organic matter during the P adsorption process. Previous studies indicated that WTS is an effective adsorbent for P but also releases organic matter, which may affect the organoleptic properties of treated water, but no study has characterised organic release and conducted an in-depth study on its behaviours. This study characterised the organic release during the P adsorption process from four different WTS samples. This study also offers results from a 60-day column experiment that indicate that WTS columns effectively removed the majority of P from the 2 mg/L feed solution. The total organic carbon (TOC) release was gradually reduced from 24.9 mg/L on day 1 to stable levels of 4.4 mg/L to 4.1 mg/L from day 22 onwards. After 60 days, when the organic matter was nearly exhausted, WTS columns were still effective in P adsorption from the solution. In addition, the thermal treatment of WTS at different temperatures was investigated to reduce TOC release and increase P adsorption. The results showed that thermal treatment not only minimized TOC release but also enhanced the P adsorption capacity of the sludge. In a 24-h batch experiment, WTS treated at 600 °C showed the highest P adsorption (1.7 mg/g) with negligible TOC release when compared to sludge treated at 500 °C WTS (1.2 mg/g), 700 °C WTS (1.5 mg/g) and dried WTS (0.75 mg/g). However, the release of inorganic compounds slightly increased after thermal treatment. Future studies could focus on determining whether the thermal processing of WTS which can enhance the WTS's adsorption to emerging pollutants like per- and poly-fluoroalkyl substances and other contaminants. The findings of this study could influence the management practices of water authorities and contribute to the water sector's sustainability objectives.

Subpalpebral lavage placement for remote topical administration of ocular medications in 12 dogs: A retrospective review and assessment of owner perception.

OBJECTIVE: The aim of this study was to describe the placement of subpalpebral lavage (SPL) systems in 12 dogs (15 eyes) intolerant of topical ocular medications to assess the suitability, complications encountered and owner perception of use. ANIMALS STUDIED: Retrospective review of dogs that underwent SPL placement for treatment of ocular disease at the Ophthalmology Department, University of Bristol Small Animal Hospital between 2017 and 2021. PROCEDURE(S): Data recorded included signalment, history, diagnosis, treatment, reason for SPL placement, uni- or bilateral placement, duration of placement, complications, and outcome. Owner perception was assessed using an online questionnaire. Statistical analysis included McNemar and Wilcoxon signed-ranks tests. RESULTS: Twelve dogs (15 eyes) underwent SPL placement. Eleven owners completed the online questionnaire. Corneal ulceration was the most common disease requiring SPL placement (n = 13/15 eyes, 86.7%). Most cases received multimodal topical therapy (n = 9/15 eyes, 60.0%) via SPL. Owners administered medication 6.63 times daily via SPL (range 1-16 applications/day). All dogs requiring ongoing topical medication (n = 8/12, 66.7%) were trained to accept direct administration during SPL treatment. Statistically significant improvements in medication compliance, ease of application, and reduced perceived risk of iatrogenic ocular injury were reported by owners (p-value = .001, .004, and .031 respectively). Minor complications were infrequently reported but an excellent outcome was achieved for all eyes. CONCLUSION: Subpalpebral lavage placement provides a practical and safe solution for the provision of frequent multimodal ocular medication when treating patients with a challenging temperament.

A prospective, masked, randomized, controlled superiority study comparing the incidence of corneal injury following general anesthesia in dogs with two methods of corneal protection.

OBJECTIVE: To compare the incidence of corneal injury during general anesthesia (GA) and the immediate post-operative period in eyes protected with topical ocular lubricant alone with eyes protected with topical lubricant followed by complete eyelid closure using tape. ANIMALS STUDIED: One hundred client-owned dogs (200 eyes) undergoing GA for MRI scan. METHODS: Patients had ocular lubricant applied to both eyes upon induction of anesthesia. One eye was taped closed immediately after induction for the duration of anesthesia using Strappal® tape (BSN medical™; treatment group), and the other eye was not taped (control group). Eyes were randomly allocated to a treatment group. Ophthalmic examination was performed before and after anesthesia; the examiner was masked to eye treatment groups. Corneal injury was defined as corneal ulceration or corneal erosion. A McNemar's test was used to compare the incidence of corneal injury between groups. A paired-samples t-test was used to compare Schirmer-1 tear test (STT-1) readings between groups. RESULTS: Sixteen eyes (8%) developed corneal erosion. No corneal ulceration occurred. There was no significant difference between incidence of corneal erosion between groups (p = .454). There was a significant decrease in STT-1 readings following GA in both groups (p < .001), with no significant difference in STT-1 between groups (p = .687). No adverse effects of taping the eye closed were observed. CONCLUSION: Taping the eyes closed during GA had no additional benefit to the lubrication protocol used in this study.

Mobile EEG reveals functionally dissociable dynamic processes supporting real-world ambulatory obstacle avoidance: Evidence for early proactive control.

The ability to safely negotiate the world on foot takes humans years to develop, reflecting the extensive cognitive demands associated with real-time planning and control of walking. Despite the importance of walking, methodological limitations mean that surprisingly little is known about the neural and cognitive processes that support ambulatory motor control. Here, we report mobile EEG data recorded from 32 healthy young adults during real-world ambulatory obstacle avoidance. Participants walked along a path while stepping over expected and unexpected obstacles projected on the floor, allowing us to capture the dynamic oscillatory response to changes in environmental demands. Compared to obstacle-free walking, time-frequency analysis of the EEG data revealed clear neural markers of proactive and reactive forms of movement control (occurring before and after crossing an obstacle), visible as increases in frontal theta and centro-parietal beta power respectively. Critically, the temporal profile of changes in frontal theta allowed us to arbitrate between early selection and late adaptation mechanisms of proactive control. Our data show that motor plans are updated as soon as an upcoming obstacle appears, rather than when the obstacle is reached. In addition, regardless of whether motor plans required updating, a clear beta rebound was present after obstacles were crossed, reflecting the resetting of the motor system. Overall, mobile EEG recorded during real-world walking provides novel insight into the cognitive and neural basis of dynamic motor control in humans, suggesting new routes to the monitoring and rehabilitation of motor disorders such as dyspraxia and Parkinson's disease.

Assessing geriatric patients with head injury in the emergency department using the novel level III trauma protocol.

INTRODUCTION: Intracranial injury in elderly patients presenting with minor head trauma is often overlooked in the emergency department (ED). Our suburban community-based level II trauma hospital developed and implemented the level III trauma protocol (L3TP) in January 2016 to better evaluate and diagnose intracranial injury in elderly patients presenting with minor head trauma after a fall. The L3TP requires that the ED physician immediately assess all patients meeting the following criteria 1) Age ≥ 65 years old. 2) Currently taking any anticoagulant or antiplatelet agents. 3) Presenting in the ED with a potential head injury after a fall. The ED physician determines if these high-risk patients require emergent imaging, obviating the need for trauma team activation unless an intracranial hemorrhage (ICH) is found. The purpose of this study was to assess the impact of the novel L3TP on resource utilization and patient outcome. METHODS: Our retrospective cohort study included patients who met the L3TP inclusion criteria and had an ICH diagnosed by non-contrast computed tomography (CT). We compared patients triaged by the L3TP (January to December 2017) to patients triaged before the L3TP was implemented (January to August 2015) in order to assess the impact of the L3TP on resource utilization and patient outcome. The data was analyzed using two independent samples t-tests and Chi-square tests. RESULTS: Patients triaged by the L3TP had a significantly shorter average length of time from arrival in the ED to CT (level III trauma 0.64 h vs control 2.37 h, (d = 1.73; 95% CI = 1.42, 2.04), p ≤ 0.0001) and ED length of stay (level III trauma 2.55 h vs control 4.72 h, (d = 2.17; 95% CI = 1.21, 3.13), p ≤ 0.0001). There was insufficient evidence to conclude that there was any difference in health outcomes between the control and level III trauma groups. CONCLUSION: The L3TP is an effective and resource efficient protocol that quickly identifies ICH in elderly patients without activating the trauma team for every elderly patient presenting to the ED with a potential head injury after a fall.

Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia.

BIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical nuclear factor-κB pathway is active in BIRC3-mutated cell lines and in primary CLL samples, as documented by the stabilization of MAP3K14 and by the nuclear localization of p52. In addition, BIRC3-mutated primary CLL cells are less sensitive to flu-darabine. In order to confirm in patients that BIRC3 mutations confer resistance to fludarabine-based chemoimmunotherapy, a retrospective multicenter cohort of 287 untreated patients receiving first-line FCR was analyzed by targeted next-generation sequencing of 24 recurrently mutated genes in CLL. By univariate analysis adjusted for multiple comparisons BIRC3 mutations identify a poor prognostic subgroup of patients in whom FCR treatment fails (median progression-free survival: 2.2 years, P<0.001) similar to cases harboring TP53 mutations (median progression-free survival: 2.6 years, P<0.0001). BIRC3 mutations maintained an independent association with an increased risk of progression with a hazard ratio of 2.8 (95% confidence interval 1.4-5.6, P=0.004) in multivariate analysis adjusted for TP53 mutation, 17p deletion and IGHV mutation status. If validated, BIRC3 mutations may be used as a new molecular predictor to select high-risk patients for novel frontline therapeutic approaches.

The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis.

Prion diseases are a unique group of infectious chronic neurodegenerative disorders to which there are no cures. Although prion infections do not stimulate adaptive immune responses in infected individuals, the actions of certain immune cell populations can have a significant impact on disease pathogenesis. After infection, the targeting of peripherally-acquired prions to specific immune cells in the secondary lymphoid organs (SLO), such as the lymph nodes and spleen, is essential for the efficient transmission of disease to the brain. Once the prions reach the brain, interactions with other immune cell populations can provide either host protection or accelerate the neurodegeneration. In this review, we provide a detailed account of how factors such as inflammation, ageing and pathogen co-infection can affect prion disease pathogenesis and susceptibility. For example, we discuss how changes to the abundance, function and activation status of specific immune cell populations can affect the transmission of prion diseases by peripheral routes. We also describe how the effects of systemic inflammation on certain glial cell subsets in the brains of infected individuals can accelerate the neurodegeneration. A detailed understanding of the factors that affect prion disease transmission and pathogenesis is essential for the development of novel intervention strategies.

Detecting the neural correlates of episodic memory with mobile EEG: Recollecting objects in the real world.

Episodic memory supports recognition of the details of complex real world experiences, providing a continuous record of events embedded within spatial and temporal context. Despite the inherently dynamic nature of real events, the bulk of neuroscientific research to date examines recognition in absence of the detailed contextual information that is known to be a defining characteristic. Given the importance of environmental context for episodic memory, examining ERP correlates of memory in more naturalistic settings is vital for progress in understanding how retrieval operates in daily life. The current study capitalized on recent advances in mobile EEG technology to address this issue and is the first to investigate ERP correlates of episodic retrieval in real world contexts. Participants were guided around a pre-defined route inside a building on campus, while performing a recognition memory task, which paired images of objects with actual physical locations in the building to provide context. Importantly, the findings clearly demonstrate that it is possible to observe reliable neural correlates of memory in real world contexts. Replicating two well established ERP correlates of episodic retrieval reported in prior laboratory based studies, we detected FN400 old/new effects traditionally associated with familiarity between 300 and 500 ms, and a late posterior negativity (LPN) often linked to reconstructive processing or evaluation of retrieval outcomes between 500 and 800 ms. Moreover, the FN400 effect was found to be sensitive to retrieval of context, with more sustained effects for objects encountered in a different context at study and test. Overall, the current work highlights the power of mobile EEG technology for examining complex cognitive functions in more naturalistic real world settings.

Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility.

Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5+ CD11c+ cells.

Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. muris in resistant mouse strains is associated with the induction of a protective T helper cell type 2 (Th2)-polarized immune response. Susceptible mouse strains, in contrast, mount an inappropriate Th1 response to T. muris infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5-expressing cells towards the B-cell follicles. Previous studies using a complex in vivo depletion model have suggested that CXCR5-expressing conventional dendritic cells (cDC) help regulate the induction of Th2-polarized responses. Here, transgenic mice with CXCR5 deficiency specifically restricted to CD11c+ cells were used to determine whether the specific absence CXCR5 on CD11c+ cells such as cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 balance. We show that in contrast to control mice, those which lacked CXCR5 expression on CD11c+ cells failed to clear T. muris infection and developed cytokine and antibody responses that suggested a disturbed Th1/Th2 balance with enhanced IFN-γ expression. These data suggest an important role of CXCR5-expressing CD11c+ cells such as cDC in immunity to oral T. muris infection.

Nevus of Ota (oculodermal melanocytosis) in a dog.

A 5-year-old, female, spayed Rhodesian Ridgeback presented with ocular melanocytosis and skin hyperpigmentation involving the distribution of the first and second divisions of the trigeminal nerve on the right side of the face. The dermatomal pattern of the hyperpigmentation was similar to nevus of Ota or oculodermal melanocytosis reported in humans. This condition has been associated with increased risk of developing secondary glaucoma and melanoma transformation in skin, ocular, orbital tissues, and the central nervous system. The clinical investigation and description of oculodermal melanocytosis (nevus of Ota) are presented for the first time in the dog.

Use of a 350-mm2 Baerveldt glaucoma drainage device to maintain vision and control intraocular pressure in dogs with glaucoma: a retrospective study (2013-2016).

OBJECTIVE: To evaluate the 350-mm2 Baerveldt glaucoma drainage device (GDD) in dogs with refractory glaucoma when modifications to address postoperative hypotony (extraluminal ligature; intraluminal stent) and the fibroproliferative response (intraoperative Mitomycin-C; postoperative oral colchicine and prednisolone) are implemented as reported in human ophthalmology. DESIGN: Retrospective case series. ANIMALS: Twenty-eight client-owned dogs (32 eyes) including seven dogs (nine eyes) with primary glaucoma and 21 dogs (23 eyes) with secondary glaucoma. METHODS: The medical records of all dogs undergoing placement of a 350-mm2 Baerveldt GDD at a veterinary ophthalmology referral service between 2013 and 2016 were reviewed. Signalment, diagnosis, duration and previous treatment of glaucoma, previous intraocular surgery, IOP, visual, and surgical outcomes were recorded. RESULTS: IOP was maintained <20mmHg in 24 of 32 (75.0%) eyes. Fourteen eyes (43.8%) required no adjunctive treatments to maintain this IOP control. Fewer doses of glaucoma medication were required following surgery. Vision was retained in 18 of 27 (66.7%) eyes with vision at the time of surgery. No eyes that were blind at the time of surgery (n = 5) had restoration of functional vision. Complications following surgery included hypotony (26/32; 81.3%), intraocular hypertension (24/32; 75.0%), and fibrin formation within the anterior chamber (20/32; 62.5%). The average follow-up after placement of the GDD was 361.1 days (median 395.6 days). CONCLUSION: Efforts to minimize postoperative hypotony and address the fibroproliferative response following placement of a 350-mm2 Baerveldt GDD showed an increased success rate to other reports of this device in dogs and offers an alternative surgical treatment for controlling intraocular pressure in dogs with glaucoma.

Investigating the relationship between implicit and explicit memory: Evidence that masked repetition priming speeds the onset of recollection.

Memory theories assume that unconscious processes influence conscious remembering, but the exact nature of the relationship between implicit and explicit memory remains an open question. Within the context of episodic recognition tests research typical shows that priming impacts behavioral and neural indices of familiarity. By this account, implicit memory leads to enhanced fluency of processing, which is then attributed to 'oldness' in the context of recognition judgments. Recently, however, behavioral and neuroimaging evidence has emerged to suggest that priming can also influence recollection, suggesting that the rate of recollection increases following priming. Here, we examine the relationship between priming and recollection, using Event-Related Potentials (ERPs) to assess changes in the timecourse of processing. Participants studied a series of words, and episodic memory was assessed using a standard item recognition test, but masked repetition priming preceded half of the test cues. Results confirmed that implicit memory was engaged: priming produced robust facilitation of recognition Reaction Times (RTs), with larger effects for studied than unstudied words. Mapping onto the RT data, ERPs recorded during recognition testing over centro-parietal electrodes revealed N400-like priming effects (250-500ms) that were larger in magnitude for studied than unstudied words. More importantly, priming also had a clear impact on explicit memory, as measured by recollection-related left-parietal old/new effects. While old/new effects for unprimed trials were present during the typical 500-800ms latency interval, the old/new effects seen for primed trials were equivalent in magnitude and topography, but onset ~300ms earlier. ERPs reveal that repetition priming speeds the onset of recollection, providing a novel demonstration that unconscious memory processes can have a measureable, functional, influence on conscious remembering.

The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis.

Prion diseases are a unique group of transmissible, chronic, neurodegenerative disorders. Following peripheral exposure (e.g. oral), prions often accumulate first within the secondary lymphoid tissues before they infect the central nervous system (CNS). Prion replication within secondary lymphoid tissues is crucial for the efficient spread of disease to the CNS. Once within the CNS, the responses of innate immune cells within it can have a significant influence on neurodegeneration and disease progression. Recently, there have been substantial advances in our understanding of how cross-talk between the host and the vast community of commensal microorganisms present at barrier surfaces such as the gut influences the development and regulation of the host's immune system. These effects are evident not only in the mucosal immune system in the gut, but also in the CNS. The actions of this microbial community (the microbiota) have many important beneficial effects on host health, from metabolism of nutrients and regulation of host development to protection from pathogen infection. However, the microbiota can also have detrimental effects in some circumstances. In this review we discuss the many and varied interactions between prions, the host and the gut microbiota. Particular emphasis is given to the ways by which changes to the composition of the commensal gut microbiota or congruent pathogen infection may influence prion disease pathogenesis and/or disease susceptibility. Understanding how these factors influence prion pathogenesis and disease susceptibility is important for assessing the risk to infection and the design of novel opportunities for therapeutic intervention.

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis.

UNLABELLED: Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE: Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal GALT are the essential early sites of prion accumulation. Furthermore, congruent infection with a large intestinal helminth (worm) around the time of oral prion exposure did not affect disease pathogenesis. This is important for our understanding of the factors that influence the risk of prion infection and the preclinical diagnosis of disease. The detection of prions within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, our data suggest that using these biopsy specimens may miss individuals in the early stages of oral prion infection and significantly underestimate the disease prevalence.

Corneal and anterior segment foreign body trauma in dogs: a review of 218 cases.

OBJECTIVES: To review clinical data on dogs that suffered a corneal and anterior segment foreign body (CASFB) trauma and to determine the risk factors for foreign body (FB) trauma and subsequent enucleation. ANIMALS STUDIED: Dogs with CASFB presented to the Animal Health Trust (AHT) from January 2000 to December 2012. PROCEDURES: Clinical data for CASFB cases were compared to those available for the remaining AHT ophthalmic population over the same period. The depth of the FB trauma was divided into five categories. The type of FB and method of removal were described for each category. The degree of secondary uveitis and lens involvement was graded and correlated with subsequent enucleation. RESULTS: The mean age (standard deviation) of 218 identified CASFB cases was 3.96 (2.95) years. Risk factors for CASFB trauma were dogs younger than 5 years, English Springer Spaniels, Labrador Retrievers, and working dogs. Most dogs required general anesthesia for FB removal, and hypodermic needles were the most commonly used instrument. The lens was involved in some cases with a full-thickness CASFB trauma (n = 49, 45%), but most suffered a minor lens trauma (n = 37, 76%). The lens trauma and phacoclastic uveitis were managed medically in most dogs (n = 37, 76%), and phacoemulsification was only elected as initial treatment in some dogs (n = 10, 20%). Enucleation was required overall in 6% of dogs. Statistically significant associations were found between enucleation and depth of FB trauma, degree of uveitis, and severity of lens trauma (P < 0.001). CONCLUSIONS: Young dogs, English Springer Spaniels, Labrador Retrievers, and working dogs had an increased risk of CASFB trauma. Risk factors for enucleation were full-thickness FB penetration, severe lens trauma, and severe uveitis.

The neural mechanism underlying recollection is sensitive to the quality of episodic memory: Event related potentials reveal a some-or-none threshold.

Although much is known about the underlying neural systems that support recollection, exactly how recollection operates remains unclear. One possibility is that recollection reflects the operation of a continuous retrieval process, whereby test cues always elicit some information from memory. Alternatively, recollection may reflect the operation of a thresholded process that allows for retrieval failure, whereby test cues sometimes elicit no information from memory at all. Here we demonstrate that recollection is thresholded by measuring a commonly reported electrophysiological correlate of episodic retrieval--known as the Left Parietal old/new effect. We use a novel source task designed to directly measure the accuracy of retrieval success, finding that the neural correlate of retrieval was sensitive to the precision of responses when recollection succeeded, but was absent when recollection failed. The results clarify the nature of the neural mechanism underlying episodic memory, providing novel evidence in support of some-or-none threshold models of recollection.

Aging and the mucosal immune system in the intestine.

Bacterial and viral infections of the gastrointestinal tract are more common in the elderly and represent a major cause of morbidity and mortality. The mucosal immune system provides the first line of defence against pathogens acquired by ingestion and inhalation, but its function is adversely affected in the elderly. This aging-related decline in the immune function is termed immunosenescence and is associated with diminished abilities to generate protective immunity, reduced vaccine efficacy, increased incidence of cancer, inflammation and autoimmunity, and the impaired ability to generate tolerance to harmless antigens. In this review we describe our current understanding of the effects immunosenescence has on the innate and adaptive arms of the mucosal immune system in the intestine. Current estimates suggest that by the year 2050 up to 40% of the UK population will be over 65 years old, bringing with it important health challenges. A thorough understanding of the mechanisms that contribute to the development of immunosenescence is therefore crucial to help identify novel approaches to improve mucosal immunity in the elderly.

Effect of docosahexaenoic acid supplementation on inflammatory cytokine levels in infants at high genetic risk for type 1 diabetes.

OBJECTIVE: Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic ß-cells. In this study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. RESEARCH DESIGN AND METHODS: This was a multicenter, two-arm, randomized, double-blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first 5 months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1 µg/mL. RESULTS: The levels of RBC DHA were increased by 61-100% in treated compared to control infants at ages 6-36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1ß, TNFα, or IL-12p40 at any of the six timepoints measured. The inflammatory marker, high-sensitivity C-reactive protein (hsCRP), was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at the age of 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥two persistently positive biochemical islet autoantibodies. CONCLUSIONS: This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced.