Climate, host ontogeny and pathogen structural specificity determine forest disease distribution at a regional scale

Predicting forest health at a regional level is challenging as forests are simultaneously attacked by multiple pathogens. Usually, the impacts of each pathogen are studied separately, however, interactions between them can affect disease dynamics. Pathogens can interact directly by competing for the same niche, but also facilitate or suppress each other via indirect effects through the host. We studied 66 native Mediterranean Pinus nigra stands located in the Pyrenees which were affected by two pathogens with different structural specificity: Dothistroma pini causing Dothistroma needle blight and Diplodia sapinea causing Diplodia shoot blight. We explored the ecology of both pathogens and whether the diseases they caused had an impact on trees and recruits. No signs of competition were found on adult trees. Diplodia shoot blight was restricted to the warmest and driest areas, while no climatic restrictions were identified for Dothistroma needle blight. Both diseases caused additive effects on crown defoliation and defoliated trees showed stagnated growth. In the regeneration layer, signs of disease suppression were found. In the warmest and driest areas, seedling mortality was mainly associated with Diplodia shoot blight, even though both pathogens were detected. Clear signs of D. pini spillover from canopy trees to recruits were found. However, seedling mortality caused by Dothistroma needle blight was only restricted to the coldest and wettest sites where D. sapinea could not survive. Large crowns in adult trees probably allow both pathogens to co-exist and cause additive impacts. The smaller size of recruits and a higher susceptibility to environmental stress compared to adult trees probably facilitates the effects of Diplodia shoot blight which masked those caused by Dothistroma needle blight. By considering climatic constraints, host ontogeny and structural specificity, we could dissect the disease impacts of two different pathogens and successfully explain forest health at a regional scale

Halophytophthora fluviatilis Pathogenicity and Distribution along a Mediterranean-Subalpine Gradient

Halophytophthora species have been traditionally regarded as brackish water oomycetes; however, recent reports in inland freshwater call for a better understanding of their ecology and possible pathogenicity. We studied the distribution of Halophytophthora fluviatilis in 117 forest streams by metabarcoding river filtrates taken in spring and autumn and by direct isolation from floating leaves. Pathogenicity on six Fagaceae species and Alnus glutinosa was assessed by stem inoculations. The distribution of H. fluviatilis was correlated with high mean annual temperatures (>93.5% of reports in Ta > 12.2 degrees C) and low precipitation records. H. fluviatilis was therefore widely distributed in forest streams in a warm-dry climate, but it was mostly absent in subalpine streams. H. fluviatilis was primarily detected in autumn with few findings in spring (28.4% vs. 2.7% of streams). H. fluviatilis was able to cause small lesions on some tree species such as Quercus pubescens, Q. suber and A. glutinosa. Our findings suggest that H. fluviatilis may be adapted to warm and dry conditions, and that it does not pose a significant threat to the most common Mediterranean broadleaved trees

Pathogenicity of Phytophthora and Halophytophthora species on black alder and the host histological response

Riparian alder forests are threatened by Phytophthora across Europe. Comparative studies of the pathogenicity of Phytophthora species are crucial for developing effective management strategies. Although only a limited number of species, particularly P. × alni, lead to tree decline in natural environments, many species demonstrate pathogenicity in inoculation trials. Phytophthora species vary in their ability to infect different tissues, such as phloem and xylem, and trigger defence responses in the host through the formation of tyloses and callose. By comparing the histological responses of alder to various Phytophthora species, we can gain insights into the success of P. × alni and the potential damage that could be caused by other species. To investigate the defence strategies of black alder (Alnus glutinosa) against attack by Phytophthora and Halophytophthora species present in Catalonia (NE Spain), we conducted inoculation trials on saplings using nine potentially pathogenic species and compared the histological responses. Phytophthora × alni and P. plurivora were the most aggressive species followed by other exotic species such as P. × cambivora and P. cactorum. Phytophthora × alni and P. plurivora were equally damaging despite the higher prevalence of P. × alni in declining alders in natural settings. Although P. × alni mainly invaded the phloem, P. plurivora also invaded the xylem and triggered the production of tyloses. Histological analyses revealed a diverse range of plant responses to infection by Phytophthora species, providing a better understanding of their adaptability in natural environments compared with solely observing lesions. The low level of callose production in saplings inoculated with P. × alni compared with callose production in saplings inoculated with less pathogenic species suggests that P. × alni can evade recognition by the host and, hence, could partially explain its success

Nationwide COVID-19-EII Study: Incidence, Environmental Risk Factors and Long-Term Follow-Up of Patients with Inflammatory Bowel Disease and COVID-19 of the ENEIDA Registry

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD

Effectiveness, cost-utility, and benefits of a multicomponent therapy to improve the quality of life of patients with fibromyalgia in primary care : a mixed methods study protocol

Introduction:Fibromyalgia (FM) is a chronic condition characterized by chronic pain, fatigue and loss of function which significantly impairs quality of life. Although treatment of FM remains disputed, some studies point at the efficacy of interdisciplinary therapy. This study aims to analyze the effectiveness, cost-utility and benefits of a multicomponent therapy on quality of life (main variable), functional impact, mood and pain in people suffering from FM that attend primary care centers (PCCs) of the Catalan Institute of Health (ICS).Methods and analysis:A 2-phase, mixed methods study has been designed following Medical Research Council guidance. Phase 1: Pragmatic randomized clinical trial with patients diagnosed with FM that attend one of the 11 PCCs of the ICS Gerència Territorial Terres de l'Ebre. We estimate a total sample of 336 patients. The control group will receive usual clinical care, while the multicomponent therapy group (MT group) will receive usual clinical care plus group therapy (consisting of health education, exercise and cognitive-behavioural therapy) during 12 weeks in 2-hourly weekly sessions. Analysis: the standardized mean response and the standardized effect size will be assessed at 3, 9, and 15 months after the beginning of the study using multiple linear regression models. Utility measurements will be used for the economic analysis. Phase 2: Qualitative socio constructivist study to evaluate the intervention according to the results obtained and the opinions and experiences of participants (patients and professionals). We will use theoretical sampling, with 2 discussion groups of participants in the multicomponent therapy and 2 discussion groups of professionals of different PCCs. A thematic content analysis will be carried out.Ethics and dissemination:This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P18/068). Articles will be published in international, peer-reviewed scientific journals.Trial registration:Clinical-Trials.gov: NCT04049006

Neurotrophin receptor p75NTR mediates Huntington's disease-associated synaptic and memory dysfunction

Learning and memory deficits are early clinical manifestations of Huntington's disease (HD). These cognitive impairments have been mainly associated with frontostriatal HD pathology; however, compelling evidence provided by several HD murine models suggests that the hippocampus may contribute to synaptic deficits and memory dysfunction in HD. The neurotrophin receptor p75(NTR) negatively regulates spine density, which is associated with learning and memory; therefore, we explored whether disturbed p75(NTR) function in the hippocampus could contribute to synaptic dysfunction and memory deficits in HD. Here, we determined that levels of p75(NTR) are markedly increased in the hippocampus of 2 distinct mouse models of HD and in HD patients. Normalization of p75(NTR) levels in HD mutant mice heterozygous for p75(NTR) prevented memory and synaptic plasticity deficits and ameliorated dendritic spine abnormalities, likely through normalization of the activity of the GTPase RhoA. Moreover, viral-mediated overexpression of p75(NTR) in the hippocampus of WT mice reproduced HD learning and memory deficits, while knockdown of p75(NTR) in the hippocampus of HD mice prevented cognitive decline. Together, these findings provide evidence of hippocampus-associated memory deficits in HD and demonstrate that p75(NTR) mediates synaptic, learning, and memory dysfunction in HD

Effectiveness, cost-utility, and benefits of a multicomponent therapy to improve the quality of life of patients with fibromyalgia in primary care: A mixed methods study protocol

Introduction: Fibromyalgia (FM) is a chronic condition characterized by chronic pain, fatigue and loss of function which significantly impairs quality of life. Although treatment of FM remains disputed, some studies point at the efficacy of interdisciplinary therapy. This study aims to analyze the effectiveness, cost-utility and benefits of a multicomponent therapy on quality of life (main variable), functional impact, mood and pain in people suffering from FM that attend primary care centers (PCCs) of the Catalan Institute of Health (ICS). Methods and analysis: A 2-phase, mixed methods study has been designed following Medical Research Council guidance. Phase 1: Pragmatic randomized clinical trial with patients diagnosed with FM that attend one of the 11 PCCs of the ICS Gerència Territorial Terres de l'Ebre. We estimate a total sample of 336 patients. The control group will receive usual clinical care, while the multicomponent therapy group (MT group) will receive usual clinical care plus group therapy (consisting of health education, exercise and cognitive-behavioural therapy) during 12 weeks in 2-hourly weekly sessions. Analysis: the standardized mean response and the standardized effect size will be assessed at 3, 9, and 15 months after the beginning of the study using multiple linear regression models. Utility measurements will be used for the economic analysis. Phase 2: Qualitative socio constructivist study to evaluate the intervention according to the results obtained and the opinions and experiences of participants (patients and professionals). We will use theoretical sampling, with 2 discussion groups of participants in the multicomponent therapy and 2 discussion groups of professionals of different PCCs. A thematic content analysis will be carried out. Ethics and dissemination: This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P18/068). Articles will be published in international, peer-reviewed scientific journals

Falls predict acute hospitalization in Parkinson's disease

Background: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit. Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH. Conclusion: Falls is an independent predictor of AH in PD patients