Pediatric non-galenic pial arteriovenous fistula's characteristics and outcomes: a systematic review.

INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.

Estimation of sensitivity and specificity of bulk tank milk PCR and 2 antibody ELISA tests for herd-level diagnosis of Mycoplasma bovis infection using Bayesian latent class analysis.

Mycoplasmosis (due to infection with Mycoplasma bovis) is a serious disease of beef and dairy cattle that can adversely impact health, welfare and productivity (Maunsell et al. (2011)). Mycoplasmosis can lead to a range of often severe, clinical presentations. Mycoplasma bovis (M. bovis) infection can present either clinically or subclinically, with the potential for recrudescence of shedding in association with stressful periods. Infection can be maintained within herds because of intermittent shedding (Calcutt et al., 2018, Hazelton et al., 2018). M. bovis is recognized as poorly responsive to treatment which represents a major challenge for control in infected herds. Given this, particular focus is needed on biosecurity measures to prevent introduction into uninfected herds in the first place. A robust and reliable laboratory test for surveillance is important both for herd-level prevention and control. The objective of this study was to estimate the sensitivity and specificity of 3 diagnostic tests (one PCR and 2 ELISA tests) on bulk tank milk, for the herd-level detection of M. bovis using Bayesian latent class analysis. In autumn 2018, bulk tank milk samples from 11,807 herds, covering the majority of the main dairy regions in Ireland had been submitted to the Department of Agriculture testing laboratory for routine surveillance were made available. A stratified random sample approach was used to select a cohort of herds for testing from this larger sample set. A final study population of 728 herds had bulk tank milk samples analyzed using a Bio-X ELISA (ELISA 1), an IDvet ELISA (ELISA 2) and a PCR test. A Bayesian latent class analysis (BLCA) was conducted to estimate the sensitivity (Se) and specificity (Sp) of the 3 diagnostic tests applied to bulk tank milk (BTM) for the detection of the herd-level infection. An overall LCA was conducted on all herds within a single population (a 3-test, 1-population model). The herds were also split into 2 populations based on herd size (small herds had < 82 cattle) (a 3-test, 2-population model) and separately into 3 regions in Ireland (Leinster, Munster and Connacht/Ulster) (a 3-test, 3-population model). The latent variable of interest was the herd-level M. bovis infection status. In total, 363/728 (50%) were large herds, 7 (1.0%) were positive on PCR, 88 (12%) positive on ELISA 1, and 406 (56%) positive on ELISA 2. Based on the 2-population model, the sensitivity (95% Bayesian credible interval (BCI) was 0.03 (0.02, 0.05), 0.22 (0.18, 0.27), 0.94 (0.88, 0.98) for PCR, ELISA 1 and ELISA 2 respectively. The specificity (95% BCI) was 0.99 (0.99, 1.0), 0.97 (0.95, 0.99), and 0.92 (0.86, 0.97) for PCR, ELISA 1 and ELISA 2 respectively. The herd-level true prevalence was estimated at 0.43 (BCI 0.35, 0.5) for smaller herds. The true prevalence was estimated at 0.62 (BCI 0.55, 0.69) for larger herds. The true prevalence was estimated at 0.56 (BCI 0.49, 0.463) in the 1-population model. For the 3-population model, the sensitivity (95% BCI) was 0.03 (0.02, 0.05), 0.24 (0.18, 0.29), 0.95 (0.9, 0.98) for PCR, ELISA 1 and ELISA 2 respectively. The specificity (95% BCI) was 0.99 (0.99, 1.0), 0.98 (0.96, 0.99), and 0.88 (0.79, 0.95) for PCR, ELISA 1 and ELISA 2 respectively. The herd-level true prevalence (95% BCI) was estimated at 0.65 (0.56, 0.73), 0.38 (0.28, 0.46) and 0.53 (0.4, 0.65) for population 1, 2, 3 respectively. Across all 3 models, the range in true prevalence was 38% to 65% of Irish dairy herds infected with M. bovis. The operating characteristics vary substantially between tests. The IDvet ELISA had a relatively high Se (the highest Se of the 3 tests studied) but it was estimated at 0.95 at its highest in 3-test, 3-population model. This test may be an appropriate test for herd-level screening or prevalence estimation within the context of the endemically infected Irish dairy cattle population. Further work is required to optimize this test and its interpretation when applied at herd-level to offset concerns related to the lower than optimal test Sp.

Legal Minors Who Inject: Differences in Socio-Demographics and Treatment Needs Compared to Adults in a Swedish National Sample of People with Injecting Drug Use.

BACKGROUND: Injection drug use among legal minors is under-researched. Although the population may be small in absolute terms, treatment needs may be greater than for those who began injecting as adults. Such knowledge may help tailor services more effectively. Previous research tends to use selective samples or focuses solely on medical indicators. The present study uses a larger sample drawn from national register data in Sweden over a 9-year period (2013-2021) to analyze differences in medical and social treatment needs between people who began injecting as legal minors and their older counterparts. METHOD: Data on first-time visitors to needle and syringe programmes (n = 8225, mean age 37.6, 26% women) were used. Historical socio-demographics and presenting treatment needs were compared between those with a debut injecting age under 18, and those who began injecting as adults. RESULTS: The prevalence of injecting before 18 years was 29%. This group had more negative social circumstances, such as leaving school early, worse health, and greater service consumption, compared to those who began injecting as adults. In particular, they had been subjected to a greater level of control measures, such as arrest and compulsory care. CONCLUSIONS: The present study shows that there are important health and social differences between those who inject prior to 18 and those who begin injecting as adults. This raises important questions for both child protection services and harm reduction approaches for legal minors who inject, who still qualify as 'children' in a legal and policy sense.

Exposure to environmentally relevant concentrations of ambient fine particulate matter (PM2.5) depletes the ovarian follicle reserve and causes sex-dependent cardiovascular changes in apolipoprotein E null mice.

BACKGROUND: Fine particulate matter (PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. However, effects of exposure to PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. Further, we hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of PM2.5 in females. RESULTS: Hyperlipidemic apolipoprotein E (Apoe) null ovary-intact or ovariectomized female mice and testis-intact male mice were exposed to concentrated ambient PM2.5 or filtered air for 12 weeks, 5 days/week for 4 h/day using a versatile aerosol concentration enrichment system. Primordial, primary, and secondary ovarian follicle numbers were decreased by 45%, 40%, and 17%, respectively, in PM2.5-exposed ovary-intact mice compared to controls (P < 0.05). The percentage of primary follicles with granulosa cells positive for the mitosis marker Ki67 was increased in the ovaries from PM2.5-exposed females versus controls (P < 0.05), consistent with increased recruitment of primordial follicles into the growing pool. Exposure to PM2.5 increased the percentages of primary and secondary follicles with DNA damage, assessed by γH2AX immunostaining (P < 0.05). Exposure to PM2.5 increased the percentages of apoptotic antral follicles, determined by TUNEL and activated caspase 3 immunostaining (P < 0.05). Removal of the ovaries and PM2.5-exposure exacerbated the atherosclerotic effects of hyperlipidemia in females (P < 0.05). While there were statistically significant changes in blood pressure and heart rate variability in PM2.5-compared to Air-exposed gonad-intact males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods. CONCLUSIONS: These results demonstrate that subchronic PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles. Further, PM2.5 exposure and removal of the ovaries each increase atherosclerosis progression in Apoe-/- females. Premature loss of ovarian function is associated with increased risk of osteoporosis, cardiovascular disease and Alzheimer's disease in women. Our results thus support possible links between PM2.5 exposure and other adverse health outcomes in women.

Postoperative surgical site infection rate in patients with diabetes following Mohs micrographic surgery: a retrospective analysis.

BACKGROUND: Incidence of surgical site infection (SSI) following Mohs micrographic surgery (MMS) amongst patients with diabetes is largely unknown. OBJECTIVE: Evaluate diabetes as a potential SSI risk factor in MMS by comparing SSI incidence in a cohort of patients with and without diabetes. METHODS: A 5-year retrospective review to determine SSI rate in patients with diabetes compared to patients without diabetes. SSI incidence in patients with diabetes was further compared by A1c, and the impact of antibiotics on SSI rate was also examined. RESULTS: Overall rate of SSI was 1.47% (53/3597 cases). SSI rate amongst patients with diabetes was 1.95% (14/719 cases) compared to 1.35% (39/2878 cases) in patients without diabetes, with a non-significant odds ratio for SSI of 1.45 (95% CI = 0.78-2.68, P = 0.241). Multivariable logistic regression analysis revealed no difference in SSI. Stratification of diabetic patients by A1c into ≥7.0 and <7.0 compared to patients without diabetes yielded no statistically significant difference in SSI amongst all groups (P = 0.815). Whether an antibiotic was prescribed did not significantly impact SSI rate between groups. CONCLUSION: No significant difference in postoperative SSI was found in patients with diabetes compared to patients without diabetes following MMS regardless of degree of glycaemic control.

Population structure, intergroup interaction, and human contact govern infectious disease impacts in mountain gorilla populations.

Infectious zoonotic diseases are a threat to wildlife conservation and global health. They are especially a concern for wild apes, which are vulnerable to many human infectious diseases. As ecotourism, deforestation, and great ape field research increase, the threat of human-sourced infections to wild populations becomes more substantial and could result in devastating population declines. The endangered mountain gorillas (Gorilla beringei beringei) of the Virunga Massif in east-central Africa suffer periodic disease outbreaks and are exposed to infections from human-sourced pathogens. It is important to understand the possible risks of disease introduction and spread in this population and how human contact may facilitate disease transmission. Here we present and evaluate an individual-based, stochastic, discrete-time disease transmission model to predict epidemic outcomes and better understand health risks to the Virunga mountain gorilla population. To model disease transmission we have derived estimates for gorilla contact, interaction, and migration rates. The model shows that the social structure of gorilla populations plays a profound role in governing disease impacts with subdivided populations experiencing less than 25% of the outbreak levels of a single homogeneous population. It predicts that gorilla group dispersal and limited group interactions are strong factors in preventing widespread population-level outbreaks of infectious disease after such diseases have been introduced into the population. However, even a moderate amount of human contact increases disease spread and can lead to population-level outbreaks.

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s-1). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy⋅s-1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.

Seroprevalence of Mycoplasma bovis in bulk milk samples in Irish dairy herds and risk factors associated with herd seropositive status.

Mycoplasma bovis is a serious disease of cattle worldwide; mastitis, pneumonia, and arthritis are particularly important clinical presentations in dairy herds. Mycoplasma bovis was first identified in Ireland in 1994, and the reporting of Mycoplasma-associated disease has substantially increased over the last 5 years. Despite the presumed endemic nature of M. bovis in Ireland, there is a paucity of data on the prevalence of infection, and the effect of this disease on the dairy industry. The aim of this observational study was to estimate apparent herd prevalence for M. bovis in Irish dairy herds using routinely collected bulk milk surveillance samples and to assess risk factors for herd seropositivity. In autumn 2018, 1,500 herds out of the 16,858 herds that submitted bulk tank milk (BTM) samples to the Department of Agriculture testing laboratory for routine surveillance were randomly selected for further testing. A final data set of 1,313 sampled herds with a BTM ELISA result were used for the analysis. Testing was conducted using an indirect ELISA kit (ID Screen Mycoplasma bovis). Herd-level risk factors were used as explanatory variables to determine potential risk factors associated with positive herd status (reflecting past or current exposure to M. bovis). A total of 588 of the 1,313 BTM samples were positive to M. bovis, providing an apparent herd prevalence of 0.45 (95% CI: 0.42, 0.47) in Irish dairy herds in autumn 2018. Multivariable analysis was conducted using logistic regression. The final model identified herd size, the number of neighboring farms, in-degree and county as statistically significant risk factors for herd BTM seropositivity to M. bovis. The results suggest a high apparent herd prevalence of seropositivity to M. bovis, and evidence that M. bovis infection is now endemic in the Irish dairy sector. In addition, risk factors identified are closely aligned to what we would expect of an infectious disease. Awareness raising and education about this important disease is warranted given the widespread nature of exposure and likely infection in Irish herds. Further work on the validation of diagnostic tests for herd-level diagnosis should be undertaken as a matter of priority.

Detrimental impacts of mixed-ion radiation on nervous system function.

Galactic cosmic radiation (GCR), composed of highly energetic and fully ionized atomic nuclei, produces diverse deleterious effects on the body. In researching the neurological risks of GCR exposures, including during human spaceflight, various ground-based single-ion GCR irradiation paradigms induce differential disruptions of cellular activity and overall behavior. However, it remains less clear how irradiation comprising a mix of multiple ions, more accurately recapitulating the space GCR environment, impacts the central nervous system. We therefore examined how mixed-ion GCR irradiation (two similar 5-6 beam combinations of protons, helium, oxygen, silicon and iron ions) influenced neuronal connectivity, functional generation of activity within neural circuits and cognitive behavior in mice. In electrophysiological recordings we find that space-relevant doses of mixed-ion GCR preferentially alter hippocampal inhibitory neurotransmission and produce related disruptions in the local field potentials of hippocampal oscillations. Such underlying perturbation in hippocampal network activity correspond with perturbed learning, memory and anxiety behavior.

Measuring antimicrobial use on dairy farms: A method comparison cohort study.

Antimicrobial use on UK dairy farms is measured for surveillance purposes, with veterinary sales data as a proxy for use. Two other methods of recording use have been used commonly on-farm: medicine waste bins and farm medicine records. However, none of these methods has been validated to measure antimicrobial use. The objective of this research was to assess agreement between the 3 most common methods for measuring on-farm antimicrobial use with a predetermined reference method on UK dairy farms. Antimicrobial use was measured prospectively on 26 UK dairy farms using medicine waste bins into which participants placed all discarded medicine packaging for a 12-mo period. At the end of 12 mo, farm medicine records and veterinary sales data were obtained retrospectively for participating farms. The reference method used was based on pre- and poststudy inventories combined with veterinary sales data. We investigated the systematic difference between the mean on-farm antimicrobial use measured by each of the 3 methods and a reference method, using one-way repeated-measures ANOVA models. Reliability and clinical relevance of the agreement between each pair of methods was quantified using the concordance correlation coefficient (CCC) and the Bland-Altman method, respectively. When compared with the reference method, veterinary sales data had excellent reliability for injectable antimicrobials and intramammary antimicrobials [95% confidence interval (CI) of CCC > 0.90] and moderate to excellent reliability for other antimicrobials (95% CI of CCC: 0.68-0.97). Medicine waste bins had good to excellent reliability for injectable (95% CI of CCC: 0.84-0.99), and intramammary products (95% CI of CCC: 0.78-0.94) and no agreement for other forms of antimicrobial. Farm medicine records did not agree for any form of antimicrobial when compared with the reference method. The use of veterinary sales data as a proxy for on-farm antimicrobial use in the UK represented excellent statistical reliability and offered clinically good agreement with the reference method when used to measure injectable antimicrobials. This study applies to the UK context and included a relatively small number of farms. However, these results have research and policy implications, both nationally and internationally, and are essential in accurately quantifying agricultural antimicrobial use to inform both animal and human health.

Mitigation of helium irradiation-induced brain injury by microglia depletion.

BACKGROUND: Cosmic radiation exposures have been found to elicit cognitive impairments involving a wide-range of underlying neuropathology including elevated oxidative stress, neural stem cell loss, and compromised neuronal architecture. Cognitive impairments have also been associated with sustained microglia activation following low dose exposure to helium ions. Space-relevant charged particles elicit neuroinflammation that persists long-term post-irradiation. Here, we investigated the potential neurocognitive benefits of microglia depletion following low dose whole body exposure to helium ions. METHODS: Adult mice were administered a dietary inhibitor (PLX5622) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia 2 weeks after whole body helium irradiation (4He, 30 cGy, 400 MeV/n). Cohorts of mice maintained on a normal and PLX5622 diet were tested for cognitive function using seven independent behavioral tasks, microglial activation, hippocampal neuronal morphology, spine density, and electrophysiology properties 4-6 weeks later. RESULTS: PLX5622 treatment caused a rapid and near complete elimination of microglia in the brain within 3 days of treatment. Irradiated animals on normal diet exhibited a range of behavioral deficits involving the medial pre-frontal cortex and hippocampus and increased microglial activation. Animals on PLX5622 diet exhibited no radiation-induced cognitive deficits, and expression of resting and activated microglia were almost completely abolished, without any effects on the oligodendrocyte progenitors, throughout the brain. While PLX5622 treatment was found to attenuate radiation-induced increases in post-synaptic density protein 95 (PSD-95) puncta and to preserve mushroom type spine densities, other morphologic features of neurons and electrophysiologic measures of intrinsic excitability were relatively unaffected. CONCLUSIONS: Our data suggest that microglia play a critical role in cosmic radiation-induced cognitive deficits in mice and, that approaches targeting microglial function are poised to provide considerable benefit to the brain exposed to charged particles.

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is the most common form of joint disease, causing pain and disability. Previous studies have demonstrated the role of lipid mediators in OA pathogenesis. OBJECTIVES: To explore potential alterations in the plasma lipidomic profile in an established mouse model of OA, with a view to identification of potential biomarkers of pain and/or pathology. METHODS: Pain behaviour was assessed following destabilisation of the medial meniscus (DMM) model of OA (n = 8 mice) and compared to sham controls (n = 7). Plasma and knee joints were collected at 16 weeks post-surgery. Plasma samples were analysed using ultra-high performance liquid chromatography accurate mass high resolution mass spectrometry (UHPLC-HR-MS) to identify potential differences in the lipidome, using multivariate and univariate statistical analyses. Correlations between pain behaviour, joint pathology and levels of lipids were investigated. RESULTS: 24 lipids, predominantly from the lipid classes of cholesterol esters (CE), fatty acids (FA), phosphatidylcholines (PC), N-acylethanolamines (NAE) and sphingomyelins (SM), were differentially expressed in DMM plasma compared to sham plasma. Six of these lipids which were increased in the DMM model were identified as CE(18:2), CE(20:4), CE(22:6), PC(18:0/18:2), PC(38:7) and SM(d34:1). CEs were positively correlated with pain behaviour and all six lipid species were positively correlated with cartilage damage. Pathways shown to be involved in altered lipid homeostasis in OA were steroid biosynthesis and sphingolipid metabolism. CONCLUSION: We identify plasma lipid species associated with pain and/or pathology in a DMM model of OA.

Herbivory and Attenuated UV Radiation Affect Volatile Emissions of the Invasive Weed Calluna vulgaris.

Calluna vulgaris (heather) is an aggressive invasive weed on the Central Plateau, North Is., New Zealand (NZ), where it encounters different environmental factors compared to its native range in Europe, such as high ultraviolet radiation (UV) and a lack of specialist herbivores. The specialist herbivore Lochmaea suturalis (heather beetle) was introduced from the United Kingdom (UK) in 1996 as a biocontrol agent to manage this invasive weed. Like other plant invaders, a novel environment may be challenging for heather as it adjusts to its new conditions. This process of "adjustment" involves morphological and physiological changes often linked to phenotypic plasticity. The biochemical responses of exotic plants to environmental variables in their invaded range is poorly understood. The production and release of volatile organic compounds (VOCs) is essential to plant communication and highly susceptible to environmental change. This study therefore aimed to explore the VOC emissions of heather in response to different levels of UV exposure, and to feeding damage by L. suturalis. Using tunnel houses clad with UV-selective filters, we measured VOCs produced by heather under NZ ambient, 20% attenuated, and 95% attenuated solar UV treatments. We also compared VOC emissions in the field at adjacent sites where L. suturalis was present or absent. Volatiles produced by the same target heather plants were measured at four different times in the spring and summer of 2018-2019, reflecting variations in beetle's abundance, feeding stage and plant phenology. Heather plants under 95% attenuated UV produced significantly higher amounts of (E)-ß-farnesene, decanal, benzaldehyde, and benzeneacetaldehyde compared to 25% attenuated and ambient UV radiation. We also found significant differences in volatiles produced by heather plants in beetle-present versus beetle-absent sites on most sampling occasions. We also recorded a lower number of generalist herbivores on heather at sites where L. suturalis was present. Interactions between invasive plants, a novel environment, and the native communities they invade, are discussed.

Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet.

OBJECTIVE: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of 'metabolic' OA. DESIGN: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n = 30) and wild-type littermates (n = 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets. RESULTS: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups. CONCLUSIONS: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.

Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain.

Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment.

Individual variation and repeatability of corticosterone responses of little penguins (Eudyptula minor) sampled in two successive years at Oamaru, New Zealand.

Plasma corticosterone concentrations increase when birds experience a stressor, and plasma corticosterone responses to a capture and handling stressor have been measured in many species of birds. Whilst it is assumed that the reported corticosterone responses reflect the inherent sensitivity of each bird to the stressor, responses of the same birds have rarely been measured at intervals of one or more years. The current study was conducted to measure the repeatability in two successive years of corticosterone responses of little penguins (Eudyptula minor) at Oamaru, New Zealand. There was a wide range of individual corticosterone responses to capture and restraint in 96 little penguins in 2012 and 50 penguins sampled at the same time of year in 2013. There were significant repeatabilities for the ranks of corticosterone at 15, 30 and 60min (r=0.416±0.160, r=0.636±0.115 and r=0.380±0.166 respectively) and for the ranks of integrated corticosterone responses (r=0.594±0.126) for 23 birds sampled in both years. There were no significant relationships between the size of corticosterone responses and age, body weight or condition index. Mean corticosterone concentrations at 60min were 114.22±6.65ng/ml in 2012 and 116.94±6.42ng/ml in 2013. Mean corticosterone responses did not differ between two successive years and were greater than responses of other penguin species. Penguins are well suited to long term studies in which corticosterone responses are measured annually as potential measures of changing marine environmental conditions.

X-ray powder diffraction at the XRD1 beamline at LNLS.

Various upgrades have been completed at the XRD1 beamline at the Brazilian synchrotron light source (LNLS). The upgrades are comprehensive, with changes to both hardware and software, now allowing users of the beamline to conduct X-ray powder diffraction experiments with faster data acquisition times and improved quality. The main beamline parameters and the results obtained for different standards are presented, showing the beamline ability of performing high-quality experiments in transmission geometry. XRD1 operates in the 5.5-14 keV range and has a photon flux of 7.8 × 109 photons s-1 (with 100 mA) at 12 keV, which is one of the typical working energies. At 8 keV (the other typical working energy) the photon flux at the sample position is 3.4 × 1010 photons s-1 and the energy resolution ΔE/E = 3 × 10-4.

The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary.

Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to 'test and treat' those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

Post-epidemic Schmallenberg virus circulation: parallel bovine serological and Culicoides virological surveillance studies in Ireland.

BACKGROUND: Schmallenberg virus (SBV) emerged in northern-Europe in 2011 resulting in an epidemic of ruminant abortions and congenital malformations throughout the continent. In the years following the epidemic there have been reports of SBV overwintering and continued circulation in several European countries. When the population-level of immunity declines in exposed regions, re-introduction of SBV could result in further outbreaks of Schmallenberg disease. The aims of this study were to determine the SBV seroprevalence in previously exposed Irish dairy herds in 2014 and to investigate if SBV continued to circulate in these herds in the three years (2013-2015) following the Irish Schmallenberg epidemic. Whole-herd SBV serosurveillance was conducted in 26 herds before (spring) and following the 2014 vector-season (winter), and following the 2015 vector-season (winter). In spring 2014, 5,531 blood samples were collected from 4,070 cows and 1,461 heifers. In winter 2014, 2,483 blood samples were collected from 1,550 youngstock (8-10 months old) and a subsample (n = 933; 288 cows, 645 heifers) of the seronegative animals identified in the spring. Youngstock were resampled in winter 2015. Culicoides spp. were collected in 10 herds during the 2014 vector-season and analysed for SBV; a total of 138 pools (3,048 Culicoides) from 6 SBV vector species were tested for SBV RNA using real-time PCR. RESULTS: In spring 2014, animal-level seroprevalence was 62.5 % (cows = 84.7 %; heifers = 0.6 %). Within-herd seroprevalence ranged widely from 8.5 %-84.1 % in the 26 herds. In winter 2014, 22 animals (0.9 %; 10 cows, 5 heifers, 7 youngstock) originating in 17 herds (range 1-4 animals/herd) tested seropositive. In winter 2015 all youngstock, including the 7 seropositive animals in winter 2014, tested seronegative suggesting their initial positive result was due to persistence of maternal antibodies. All of the Culicoides pools examined tested negative for SBV-RNA. CONCLUSIONS: SBV appears to have recirculated at a very low level in these herds during 2013 and 2014, while there was no evidence of SBV infection in naïve youngstock during 2015. A large population of naïve animals was identified and may be at risk of infection in future years should SBV re-emerge and recirculate as it has done in continental Europe.

Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain.

OBJECTIVES: Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the potential for targeting TRPV1 receptors within the OA joint in order to produce analgesia. METHODS: The presence of TRPV1 receptors in human synovium was detected using western blotting and immunohistochemistry. In a rat model of OA, joint levels of an endogenous ligand for TRPV1, 12-hydroxy-eicosatetraenoic acid (12-HETE), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Effects of peripheral administration of the TRPV1 receptor antagonist JNJ-17203212 on afferent fibre activity, pain behaviour and core body temperature were investigated. Effects of a spinal administration of JNJ-17203212 on dorsal horn neuronal responses were studied. RESULTS: We demonstrate increased TRPV1 immunoreactivity in human OA synovium, confirming the diseased joint as a potential therapeutic target for TRPV1-mediated analgesia. In a model of OA pain, we report increased joint levels of 12-HETE, and the sensitisation of joint afferent neurones to mechanical stimulation of the knee. Local administration of JNJ-17203212 reversed this sensitisation of joint afferents and inhibited pain behaviour (weight-bearing asymmetry), to a comparable extent as systemic JNJ-17203212, in this model of OA pain, but did not alter core body temperature. There was no evidence for increased TRPV1 function in the spinal cord in this model of OA pain. CONCLUSIONS: Our data provide a clinical and mechanistic rationale for the future investigation of the therapeutic benefits of intra-articular administration of TRPV1 antagonists for the treatment of OA pain.