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Henry VIII and Winston Churchill are clinically instructive when appreciating inter-individual variability in disease expression. Both were illustrious English leaders who as young men sustained multiple traumatic brain injuries, which may (or may not) have profoundly influenced their successes and failures of later years. Both men were admired and castigated; both struggled at various times with their bodies and their minds. Ultimately, one was initially a great man who descended as a flawed leader; the other was initially a flawed man who ascended as a great leader. Their similar yet contrasting case histories define the full spectrum ("Tudor-Churchill Spectrum") of inter-individual variability in response to brain disease or injury. The Tudor-Churchill spectrum is the immense variability between individual patients and reminds us that every person is unique, deserving of individualized thought, personalized diagnosis and tailored treatment.

Circular RNAs (circRNAs) are a group of covalently closed, endogenous, non‐coding RNAs, which exist widely in human tissues including the heart. Increasing evidence has shown that cardiac circRNAs play crucial regulatory roles in cardiovascular diseases (CVDs). In this review, we aimed to provide a systemic understanding of circRNAs with a special emphasis on the cardiovascular system. We have summarized the current research on the classification, biogenesis and properties of circRNAs as well as their participation in the pathogenesis of CVDs. CircRNAs are conserved, stable and have specific spatiotemporal expression; thus, they have been accepted as a potential diagnostic marker or an incremental prognostic biomarker for CVDs.

International audience; Esca is a complex grapevine trunk disease caused by wood-rotting ascomycetes and basidiomycetes and leading to several foliar and wood symptoms. Given that the esca expression can be influenced by several environmental, physiological, and genetic factors, foliar symptoms are inconsistent in incidence and prevalence and may appear 1 year but not the following. We have previously reported a clone-dependent expression of the disease in cv Chardonnay. Owing to metabolome analysis, we could discriminate the metabolite fingerprint of green leaves collected on diseased vines of clones 76 and 95. These clone-dependent fingerprints were year-dependent in intensity and nature. The present work was conducted to determine if the clone-dependent disease expression observed is specific to Chardonnay or if it also occurs in another cultivar. A plot located in the Jura vineyard (France) and planted with both 1004 and 1026 clones of Trousseau, a cultivar highly susceptible to esca, was thus selected and studied during 2017 and 2018. A year-dependent variation of the symptoms expression was first observed and a possible relationship with rainfall is hypothesized and discussed. Moreover, a higher percentage of the clone 1026 vines expressed disease, compared to the 1004 ones, suggesting the higher susceptibility of this clone. Finally, metabolomic analyses of the remaining green leaves (i.e, without symptom expression) of partial esca-apoplectic vines allowed us to confirm a clone-dependent metabolic response to the disease. The metabolite fingerprints obtained differed in nature and intensity to those previously reported for Chardonnay and also between years.

Recent meta-analyses suggest that insomnia specifically confers risk for Alzheimer’s Disease (AD); however, the precise mechanisms by which this occurs are not well understood. In this review, we discuss candidate mechanisms linking insomnia features to AD neuropathophysiology, potentially driving increased AD risk in insomnia patients. First, we discuss epidemiological evidence tying insomnia to AD and summarize the behavioral and neurobiological features of insomnia, as well as AD pathologies. We propose that facets of hyperarousal, a central etiological feature of insomnia, act upon underlying mechanisms contributing to AD pathogenesis. Additionally, we outline how objective short sleep duration and circadian dysregulation, other key aspects of insomnia, may act as compounding pathways to exacerbate disease expression. We close with recommendations for future studies.

Introduction Illuminating neurobiological mechanisms underlying the protective effect of recently discovered common genetic resilience variants for schizophrenia is crucial for more effective prevention efforts. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects as a schizophrenia resilience mechanism. We investigated whether common genetic resilience variants might affect brain structure in similar neural circuits. Method Using structural magnetic resonance imaging, we measured the impact of an established schizophrenia polygenic resilience score (PRSResilience) on cortical volume, thickness, and surface area in 101 healthy subjects and in a replication sample of 33 224 healthy subjects (UK Biobank). Finding We observed a significant positive whole-brain correlation between PRSResilience and cortical volume in the right fusiform gyrus (FFG) (r = 0.35; P = .0004). Post-hoc analyses in this cluster revealed an impact of PRSResilience on cortical surface area. The replication sample showed a positive correlation between PRSResilience and global cortical volume and surface area in the left FFG. Conclusion Our findings represent the first evidence of a neurobiological correlate of a genetic resilience factor for schizophrenia. They support the view that schizophrenia resilience emerges from strengthening neural circuits in the ventral visual pathway and an increased capacity for the disambiguation of social and nonsocial visual information. This may aid psychosocial functioning, ameliorate the detrimental effects of subtle perceptual and cognitive disturbances in at-risk individuals, and facilitate coping with the cognitive and psychosocial consequences of stressors. Our results thus provide a novel link between visual cognition, the vulnerability-stress concept, and schizophrenia resilience models.

Asthma is a complex and heterogenous disease characterized by variability in disease expression and severity. Multiple extrapulmonary comorbidities and treatable traits are common in people with asthma, and there is an increasing appreciation of how these may complicate asthma management. This review will discuss the prevalence and impact of extrapulmonary comorbidities/risk factors or “traits,” which have been found to co-exist in asthma (obesity, symptoms of depression and/or anxiety and physical inactivity), the impact these traits have on future outcomes (including exacerbation risk and quality of life) and asthma management, and how we should target treatment in asthma when these extrapulmonary traits are present.

Background There is limited research on hypertrophic cardiomyopathy (HCM), which is the most common inherited cardiac disorder, in diverse populations, including Black individuals. Current literature lacks comprehensive data on HCM disease expression, comorbidities, and outcomes in this historically disadvantaged group. The purpose of this study was to examine structural HCM characteristics, comorbidities, and outcomes in a Black and White cohort with HCM. Methods and Results The study was a subgroup analysis from a longitudinal, prospective study on HCM, with supplemental chart review. The sample included adults (≥18 years) with a clinical diagnosis of HCM, who self‐identified as Black/African American or White. The study sample comprised 434 individuals; 57 (13.1%) were Black, and 180 (41.5%) were women. Black patients were younger than White patients, 54.6 (13.4) versus 62.5 (14.8) years, P =0.001. Black patients were more likely to have sub‐basal and diffuse hypertrophy, 22 (38.6%) versus 56 (14.9%), P P =0.017, mid‐LV obstruction, 7 (12.3%) versus 21 (5.5%), P =0.025, and cardiac fibrosis ≥15%, 10 (22.2%) versus 19 (8.8%), P =0.009, than White patients. Black patients were more likely to experience appropriate implantable cardioverter defibrillator interventions, 5 (38.5) versus 5 (6.8), P P Conclusions This study underscores the need for continued research of HCM in Black populations, including tailored approaches to diagnosis and precise evaluation of cardiac anatomy.

PURPOSE. To investigate the role of two deep-intronic ABCA4 variants, that showed a mild splice defect in vitro and can occur on the same allele as the low penetrant c.5603A>T, in Stargardt disease (STGD1).METHODS. Ophthalmic data were assessed of 18 STGD1 patients who harbored c.769-784C>T or c.4253+43G>A in combination with a severe ABCA4 variant. Subjects carrying c.[769784C>T; 5603A>T] were clinically compared with a STGD1 cohort previously published carrying c.5603A>T noncomplex. We calculated the penetrances of the intronic variants using ABCA4 allele frequency data of the general population and investigated the effect of c.769-784C>T on splicing in photoreceptor progenitor cells (PPCs).RESULTS. Mostly, late-onset, foveal-sparing STGD1 was observed among subjects harboring c.769-784C>T or c.4253+43G>A (median age of onset, 54.5 and 52.0 years, respectively). However, ages of onset, phenotypes in fundo, and visual acuity courses varied widely. No significant clinical differences were observed between the c.[769-784C>T; 5603A>T] cohort and the c.4253+43G>A or the c.5603A>T cohort. The penetrances of c.769-784C>T (20.5%-39.6%) and c.4253+43G>A (35.8%-43.1%) were reduced, when not considering the effect of yet unidentified or known factors in cis, such as c.5603A>T (identified in 7/7 probands with c.769-784C>T; 1/8 probands with c.4253+43G>A). Variant c.769-784C>T resulted in a pseudo-exon insertion in 15% of the total mRNA (i.e., similar to 30% of the c.769-784C>T allele alone).CONCLUSIONS. Two mild intronic ABCA4 variants could further explain missing heritability in late-onset STGD1, distinguishing it from AMD. The observed clinical variability and calculated reduced penetrance urge research into modifiers within and outside of the ABCA4 gene.

Captan (a trichloromethyl sulfenyl fungicide) is commonly used for control of Neonectria ditissima in apple. In New Zealand, picking and leaf scars are the main source of new infections. The captan concentrations required for wound protection of leaf scars, picking and rasp wounds was determined in planta. Fresh wounds, inoculated with N. ditissima, were sprayed with captan using a motorised knapsack (leaf scars) or hand-held spray bottles targeting the wound area (picking and rasp wounds). Captan concentrations ranged from 0 to 400% field rate (100% = 2 kg captan/ha). Wounds were sampled pre- and post-captan application for residue analyses and the remainder assessed regularly in the field for disease expression. Disease development decreased as captan concentrations increased. Approximately 2 μg captan/scar (100% field rate) was required to protect leaf scars. Four times the field rate of captan was needed for a 55 and 70% disease reduction on picking and rasp wounds, respectively. Label-rate applications of captan controlled low incidence of N. ditissima leaf-scar infections in the field in autumn, but disease control of picking scars and other large wounds might be difficult to achieve.

Blackgram or urdbean (Vigna mungo (L.) Hepper) and mungbean (Vigna radiata (L.) Wilczek) are important leguminous crops of India, Pakistan and South-East Asian Countries. India accounts largest acreage but productivity is very low due to prevalence of biotic stresses. Among the biotic stresses, Urdbean Leaf Crinkle Disease (ULCD) is considered to be one of the most serious diseases and causes yield loss up to 100%. Symptom expression was observed to be highly influenced by temperature. Threshold temperatures for symptoms expression were determined through mechanical inoculation of seeds and exposure to fixed temperature under glasshouse conditions. Typical ULCD symptoms were observed in the temperature range 25–38 °C. Disease incidence was significantly increased between temperature range 30–35 °C and reduced at 38 °C or above. Effect of temperature on ULCD was fitted to a non-linear beta model. Based on the model potential ULCD distribution has been predicted. It was evidenced that northern India and part of central India is prone to severe leaf crinkle disease during June–September (kharif season). However, disease incidence appeared to be low during March–May (summer season) crop. Predicting potential geographical areas for low disease incidence is an important component in strategic management of the disease under changing climates.

Atomic force microscopy (AFM) has recently attracted much attention due to its ability to analyze biomolecular interactions and to detect certain biomolecules, which play a crucial role in disease expression. Despite recent studies reporting AFM imaging for the analyses of biomolecules, the application of AFM-based cancer-specific biomolecule/cell detection has remained largely underexplored, especially for the early diagnosis of cancer. In this paper, we review the recent attempts, including our efforts, to analyze and detect cancer-specific biomolecules and cancer cells. We particularly focus on two AFM-based cancer diagnosis techniques: (i) AFM imaging-based biomolecular and cellular detection, (ii) AFM cantilever-based biomolecular sensing and cell analysis. It is shown that AFM-based biomolecular detection has been applied for not only early diagnosing cancer, by measuring the minute amount of cancer-specific proteins, but also monitoring of cancer progression, by correlating the amount of cancer-specific proteins with the progression of cancer. In addition, AFM-based cell imaging and detection have been employed for diagnosing cancer, by detecting cancerous cells in tissue, as well as understanding cancer progression, by characterizing the dynamics of cancer cells. This review, therefore, highlights AFM-based biomolecule/cell detection, which will pave the way for developing a fast and point-of-care diagnostic system for biomedical applications.

Hypertrophic cardiomyopathy is the second most common cause of cardiomyopathy presenting during childhood and whilst its underlying aetiology is variable, the majority of disease is caused by sarcomeric protein gene variants. Sarcomeric disease can present at any age with highly variable disease phenotype, progression and outcomes. The majority have good childhood-outcomes with reported 5-year survival rates above 80%. However, childhood onset disease is associated with considerable life-long morbidity and mortality, including a higher SCD rate during childhood than seen in adults. Management is currently focused on relieving symptoms and preventing disease-related complications, but the possibility of future disease-modifying therapies offers an exciting opportunity to modulate disease expression and outcomes in these young patients.

Grapevine red blotch virus (GRBV), the causative agent of grapevine red blotch disease, is widespread across the United States and causes a delay in ripening events in grapes. This study evaluates the effects of GRBV on Cabernet Sauvignon grape berry composition, grafted on two different rootstocks (110R and 420A) in two seasons (2016 and 2017). Total soluble solids, acidity, and anthocyanin concentrations were monitored through ripening and at harvest. Phenolic and volatile compounds were also analyzed at harvest to determine genotypic and environmental influences on disease outcome. Sugar accumulation through ripening was lower in diseased fruit (RB (+)) than healthy fruit across rootstock and season. GRBV impact was larger in 2016 than 2017, indicating a seasonal effect on disease expression. In general, anthocyanin levels and volatile compound accumulation was lower in RB (+) fruit than healthy fruit. Total phenolic composition and tannin content was higher in RB (+) fruit than healthy fruit in only 110R rootstock. Overall, GRBV impacted Cabernet Sauvignon grape composition crafted on rootstock 110R more than those crafted on rootstock 420A.

Iris yellow spot (IYS) disease in onion (Allium cepa L.) is caused by onion thrips (Thrips tabaci L.) vectored Iris yellow spot virus (IYSV). The absence of cultivars that are resistant/tolerant to thrips and/or IYS is a challenge for onion bulb and seed production worldwide. To measure selection progress for reduced/delayed IYS symptom expression in onion breeding lines after two selection cycles, selections were performed in 2011 on previously evaluated lines that exhibited a reduced symptom expression after one selection cycle. Selected plants from each line were massed in a cage and the resulted progenies were evaluated in 2013 and 2014 along with their original populations and a susceptible check&mdash, &rsquo, Rumba&rsquo, In some comparisons, the selection progress for delayed/reduced IYS symptom expression was observed for some breeding lines. Plants of most selected breeding lines exhibited less disease expression than plants of &lsquo, For some selections, a low disease severity was observed even with a relatively high number of thrips per plant. These results suggest that further improvement might be achievable with additional cycles of selection.

Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1β-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes. Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329). Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05–1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02–1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23–2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13–2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04–2.55), p = 0.030]. Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA. Funding Agencies|Psoriasisforbundet

Cassava growth in Cote d’Ivoire is affected by the variation in weather conditions and various pests and diseases. Cassava Bacterial Blight is a particularly destructive disease influenced by weather conditions which can lead to 100% yield loss. In order to provide sustainable control strategies, it is essential to understand the occurrence and the behaviour of the disease in the different ecological zones in Cote d’Ivoire. Surveys were carried out in cassava fields from 2014 to 2017 in the seven Ivorian agro-ecological zones. These fields were assessed for the disease presence/absence, the severity index (SI) and the disease incidence (DI). Weather data were provided by weather stations in Cote d’Ivoire. The results of this study showed that the disease was present in mainly the agro-ecological zones 1, 2, 3 and 4 representing the higher yield potential zones of cassava production. Disease expression was variable depending on the years and the prevalent weather conditions in each agro-ecological zone. The high SI and DI were found in the agro-ecological zones 1, 4 and 6. The disease was able to reach rates of 100% in many zones for both SI and DI with dieback incidence mainly in the agro-ecological 1, 4 and 6 zones under unfavourable (low rainfall, RH, NRD) and favourable conditions. It is therefore urgent to implement control strategies such as such as the integration of new cassava varieties, screening under different agro-ecological zones and improvement of varieties in order to provide resistant varieties to the farmers.

Psoriasis is a chronic inflammatory dermatosis affecting 1–3% of the general population. Patients with psoriasis represent a heterogeneous population with individual disease expression – different degrees and severity of skin involvement. Psoriatic lesions in particular localizations such as the face, scalp, intertriginous or palmoplantar areas significantly reduce quality of life. Patients often feel ashamed, embarrassed, or self-conscious about their symptoms. Furthermore, genital psoriasis significantly affects sexual health. Among patients with psoriasis, the prevalence of special localizations is estimated to be 23–27% on the nails, 49% on the face, 12–16% on the palms and soles, and up to 36% in intertriginous regions. Due to peculiar features of skin in these areas, adequate and specific management is required, which is discussed in this review.

The researches results for ascospore stage causative agent and disease appearing in Western Forest-steppe of Ukraine were provided.

To investigate the relationship between subfoveal choroidal thickness and disease manifestation in a series of eyes with nonexudative age-related macular degeneration (AMD).Retrospective study of eyes with nonexudative AMD. The extracellular deposits present, drusen and subretinal drusenoid deposits (SDD, pseudodrusen) along with a newly recognized form of drusen, pachydrusen, were graded and compared with choroidal thickness as determined by optical coherence tomography. Demographic and imaging information was evaluated with descriptive statistics and generalized estimating equations.There were 94 eyes of 71 patients, who had a mean age of 78.1 years. Soft drusen alone were found in 45 eyes (47.9%) and subretinal drusenoid deposit with or without drusen in 38 (40.4%). Pachydrusen, which were typically larger than 125 μm, often had an irregular outer contour, showed a scattered distribution over the posterior pole and occurred in isolation or in groups of only a few drusen were found in 11 (11.7%). The mean subfoveal choroidal thickness in the soft drusen group was 227.9 μm, in the subretinal drusenoid deposit group 167.3 μm, and in the pachydrusen group 419 μm. The differences between the groups were highly significant.Extracellular deposits, subretinal drusenoid deposits and drusen, which are on either side of the retinal pigment epithelium, respectively, are common in nonexudative AMD. A new form of drusen presentation could be differentiated from typical soft drusen and was associated with thicker choroids. Disease manifestation in nonexudative AMD seems to be associated with choroidal thickness. Each of these has potential to lead to specific forms of late AMD.

Cassava landraces were evaluated for resistance to cassava brown streak disease (CBSD) for two cropping seasons at a disease hotspot area in Naliendele, Tanzania. Based on reactions to CBSD, several landraces including Chimaje, Mfaransa and Supa B were considered to be resistant to the disease while Kikwada, Mbuyu, and Nyoka were tolerant. ANOVA revealed that the largest sum of squares (SS) (41.9–86.7%) was attributed to the genotype of the cassava landraces, while a smaller proportion of SS (8.1–38.2%) was due to genotype by environment interactions for all traits tested, which included disease symptoms, root weight, number of roots per plant and dry matter content. Environment accounted for the smallest effect (0.01–26.3%), however, the mean squares was nonetheless significant for a few genotypes, which indicated that their disease expression was indeed influenced by the environment. Increased CBSD severity was associated with low temperatures and rainfall. Increased rainfall towards harvesting led to higher root weight but lower dry matter content in the first cropping season. Correlation analysis showed that the presence of CBSD symptoms reduces the amount of usable roots, total root weight, and root dry matter content. Many resistant/tolerant landraces also had high root weight and dry matter content, and they can be used by farmers to reduce CBSD losses. The landraces described here form novel sources of CBSD resistance that can be used for breeding disease-resistant cassava varieties with superior agronomic characteristics.

We present 3 cases of patients with castration-resistant prostate cancer and bone metastases treated with Ra, belonging to our prospective and multicenter ChoPET-Rad study. All patients underwent clinical, hematological, and biochemical monitoring between each Ra administration. Initial and follow-up F-fluorocholine PET/CT and Tc-biphosphonate bone scintigraphy were performed previously and after the third Ra administration. Both techniques correctly established the response to treatment, in agreement to the biochemical response, although differences in the disease expression (concordant and discordant patterns) were found because of the different radiotracer biodistribution and molecular information derived from them.

Research into remote sensing tools for monitoring physiological stress caused by biotic and abiotic factors is critical for maintaining healthy and highly-productive plantation forests. Significant research has focussed on assessing forest health using remotely sensed data from satellites and manned aircraft. Unmanned aerial vehicles (UAVs) may provide new tools for improved forest health monitoring by providing data with very high temporal and spatial resolutions. These platforms also pose unique challenges and methods for health assessments must be validated before use. In this research, we simulated a disease outbreak in mature Pinus radiata D. Don trees using targeted application of herbicide. The objective was to acquire a time-series simulated disease expression dataset to develop methods for monitoring physiological stress from a UAV platform. Time-series multi-spectral imagery was acquired using a UAV flown over a trial at regular intervals. Traditional field-based health assessments of crown health (density) and needle health (discolouration) were carried out simultaneously by experienced forest health experts. Our results showed that multi-spectral imagery collected from a UAV is useful for identifying physiological stress in mature plantation trees even during the early stages of tree stress. We found that physiological stress could be detected earliest in data from the red edge and near infra-red bands. In contrast to previous findings, red edge data did not offer earlier detection of physiological stress than the near infra-red data. A non-parametric approach was used to model physiological stress based on spectral indices and was found to provide good classification accuracy (weighted kappa = 0.694). This model can be used to map physiological stress based on high-resolution multi-spectral data.

European canker, caused by Neonectria ditissima, is an important disease of apple in the temperate climate of southern Brazil. Monthly inoculations of this fungus were carried out on various wound types on cvs ‘Gala’ and ‘Fuji’ over two productive cycles to better understand the seasonal susceptibility of apple trees. Wound types were: bud scars (September), petal scars (October), fruit-thinning scars (November), leaf scars (from November to May), fruit-picking wound scars for ‘Gala’ (February) and ‘Fuji’ (March), and pruning wounds (June to August). One hundred plants of each cultivar were used and inoculation sites were monitored periodically for symptom expression. At each assessment, visible lesions were counted and pruned, and wounds were painted. Differences in wound susceptibility occurred throughout the year. Most lesions resulted from inoculations of pruning wounds. Inoculations performed in spring on bud and petal scars resulted in lower disease expression than inoculations later in the season.

Producción Científica, Pines are major components of native forests and plantations in Europe, where they have both economic significance and an important ecological role. Diseases of pines are mainly caused by fungal and oomycete pathogens, and can significantly reduce the survival, vigor, and yield of both individual trees and entire stands or plantations. Pine pitch canker (PPC), caused by Fusarium circinatum (Nirenberg and O’Donnell), is among the most devastating pine diseases in the world, and is an example of an emergent invasive disease in Europe. The effects of microbial interactions on plant health, as well as the possible roles plant microbiomes may have in disease expression, have been the focus of several recent studies. Here, we describe the possible effects of co-infection with pathogenic fungi and oomycetes with F. circinatum on the health of pine seedlings and mature plants, in an attempt to expand our understanding of the role that biotic interactions may play in the future of PPC disease in European nurseries and forests. The available information on pine pathogens that are able to co-occur with F. circinatum in Europe is here reviewed and interpreted to theoretically predict the effects of such co-occurrences on pine survival, growth, and yield. Beside the awareness that F. circinatum may co-occurr on pines with other pathogens, an additional outcome from this review is an updating of the literature, including the so-called grey literature, to document the geographical distribution of the relevant pathogens and to facilitate differential diagnoses, particularly in nurseries, where some of them may cause symptoms similar to those induced by F. circinatum. An early and accurate diagnosis of F. circinatum, a pathogen that has been recently introduced and that is currently regulated in Europe, is essential to prevent its introduction and spread in plantings and forests., Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (Proyect AGL2015-69370-R), Russian Foundation for Basic Research (Grant No. 17-04-01486), Portuguese Foundation for Science and Technology (PTDC/AGR-FOR/2768/2014), Ministry of Education, Youth and Sports of the Czech Republic and the European Regional Development Fund, Grant No. CZ.02.1.01/0.0/0.0/15_003/0000453., Romanian National projects PN18040105/2018 and PN19070206/2019

Background: Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Purpose: Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Methods: Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Results: Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. Conclusion: The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data.

Humans and animals are infected by multiple endogenous and exogenous viruses but few agents cause overt tissue damage. We review the circumstances which favor overt disease expression. These can include intrinsic virulence of the agent, new agents acquired from heterologous species, the circumstances of infection such as dose and route, current infection with other agents which includes the composition of the microbiome at mucosal and other sites, past history of exposure to other infections as well as the immune status of the host. We also briefly discuss promising therapeutic strategies that can expand immune response patterns that minimize tissue damaging responses to viral infections.

Footrot is a contagious disease of sheep and other small ruminants. The causative agent, Dichelobacter nodosus, is transmitted between hooves via contaminated pasture and soil. However, the bacterium cannot invade the epidermis unless it is compromised in some manner and water maceration, which follows prolonged exposure to a moist substrate, is the most common predisposing factor. Experimental infection models have been used extensively to study the aetiology, pathogenesis, treatment and prevention of footrot. In Australia, an indoor, pen-based, infection model involving standing sheep on wet mats and bandaging inoculum onto the foot has been used commonly but does not accurately represent the pasture environment and has an impact on animal welfare. Instead, we predisposed sheep on irrigated pasture and compared three methods for infecting them with D. nodosus: application of inoculum to the interdigital skin with a swab, dripping inoculum onto the interdigital skin with a pipette, and spraying inoculum onto the pasture on which the sheep grazed. We were able to establish D. nodosus infections using all three methods but selected the swab method for further use because the dose can be controlled. It was used in two field trials and infection was established in 70 %–100 % of sheep. The infection model developed in this study improves animal welfare by reducing the level of intervention. However, as the model is pasture-based, seasonal weather patterns need to be considered to ensure predisposition and disease expression. Further research will be required to understand the environmental conditions required for transmission of D. nodosus and the clinical expression of disease.