First Report of Root Rot Caused by Phytophthora lacustris on alder (Alnus lusitanica) in Spain.

Alder decline caused by Phytophthora species is considered one of Europe´s most important diseases of natural ecosystems. In Spain, P. x alni, P. uniformis, P. x multiformis and P. plurivora have been detected in association with root and collar rot in riparian alder populations (Pintos et al. 2010, 2012, 2017; Haque et al. 2014). During the active growth periods 2020-2021, a field survey of the newly designed species Alnus lusitanica (Vít et al. 2017) was carried out at the most symptomatic areas along the Miño-Sil river basin in Galicia and León (NW-Spain). Samples of bark, root, rizosphere soil of declining trees, and river water were collected. Symptoms, similar to those caused by other Phytophthora species, included low leaf density of the canopy, generally with smaller and chlorotic leaves, and branches with dry tips. In some cases, the presence of cankers on the trunk were observed (Figure 1). Necrotic lesions were transferred onto V8-PARPH, a Phytophthora selective medium. Soil and water were baited with carnation petals. Three isolates of one Phytophthora species was recovered: two from the roots of trees, and one from river water at three different sites. The isolates were transferred to V8 agar and incubated a 22ºC in the dark. Colonies had petaloid patterns, and their optimum growth temperature ranged from 25 to 30 °C. In soil extract, non-caducous, non-papillate and ovoid sporangia were produced. Sporangia averaged 41.0×29.4 µm with a length/breadth ratio of 1.39. Internal proliferation occurred (Figure 2). No sexual structures were observed . Genomic DNA was extracted from mycelium obtained from pure cultures of three Phytophthora isolates. The ITS region of the ribosomal DNA template was performed by nested PCR using DC6 (Cooke et al. 2000) and ITS4 (White et al. 1990) in the first round, and ITS6 (Cooke et al. 2000) and ITS4 in the second. The mitochondrial gene cox1 was amplified with primers CoxF4N and CoxR4N (Kroon et al. 2004). BLASTn analyses showed 100% identity to the type of P. lacustris (AF266793, 156 matching bp) for ITS, and 100% identity to the ex-type of P. lacustris (MH136916, 596 matching bp) for the cox1 sequence. Phylogenetic analysis indicated that our isolates were localized in the same evolutionary branch as P. lacustris based on consense sequences of ITS and cox1 sequences. The ITS and cox1 sequences generated in this study were deposited in GenBank with accession number OP588369 and OP548051, and one isolate isolated from root (CECT 21212) was submitted to the Spanish Type Culture Collection (Paterna, Valencia). Pathogenicity tests with isolate CECT 21212 were conducted on ten 3-year-old alders (A. lusitanica) growing in free draining 5 L pots. One shallow cut was made into the cambium at the root collar level. A colonized 5-mm mycelial agar plug, from a 7-day-old culture was inserted into every wound (mycelial surface face-down) and sealed with Parafilm®. Five control plants were inoculated with a sterile agar plug. Plants were kept in a controlled chamber at 25 ºC and 80% humidity. After a 3-week incubation period, inoculated plants showed dieback symptoms and necrosis of the inner bark tissue (Figure 3). Lesion lengths ranged from 2 to 8 cm. Control plants remained symptomless. P. lacustris was recovered from all inoculated plants, but not from the control ones. To our knowledge, this is the first report of P. lacustris causing root rot on alders in Spain. This new detection represents an increased threat to riparian alders by the presence of an additional Phytophthora species associated with alder decline, since P. lacustris can readily adapt to a wide variety of climatic conditions with the ability to infect different hosts (Nechwatal et al. 2013).

First report of Gnomoniopsis smithogilvyi causing chestnut brown rot on nuts and burrs of sweet chestnut in Spain.

About 60% of the nut production of sweet chestnut (Castanea sativa Mill.) in Europe originates in Spain (FAOSTAT, 2022), mostly (91%) in Galicia (NW Spain). In September 2021, premature fall of immature chestnut burrs and nuts of C. sativa was observed in eight orchards of Pontevedra and Ourense (provinces of Galicia). Chestnut green burrs had turned brown and fallen off, and the nuts showed brown lesions in kernels and embryos. Some nuts had become mummified. Symptomatic samples of burrs and nuts, including mummified fruits, were collected. Small pieces of samples were surface-disinfected with 2% sodium hypochlorite, and plated onto potato dextrose agar (PDA) plates. Colonies were creamy white to gray or light brown, and presented a woolly to felty mycelium with a dense development in concentric circles. Brownish to black conidiomata, produced abundantly, were globose to sub-globose. Conidia were hyaline, oval, obovoid, fusoid and multi-guttulate, and 6.6±0.78 [5.07 to 9.01] µm x 3.2±0.43 [2.41 to 4.38] µm in size. These features matched those described for Gnomoniopsis smithogilvyi (Shuttleworth et al. 2012), syn. G. castaneae (Visentin et al. 2012; Shuttleworth et al. 2015). Genomic DNA was extracted from mycelium developed in 22 burrs and nuts, and 30 pure cultures. The rDNA internal transcribed spacer (ITS), fragments of the ß-tubulin (TUB2) and the translation elongation factor-1α (TEF-1α) genes were amplified using ITS1F (Gardes and Bruns 1993) and ITS4 (White et al. 1990), T1/Bt2b (O'Donnell and Cigelnik 1997), and EF1-728F/EF1-986R (Carbone and Kohn 1999) primers, respectively. Two isolates (EFA 924A, EFA962.4A) were deposited in the Spanish Type Culture Collection (Paterna, Valencia), and their sequences submitted to GenBank (accession nos.: ITS: OM319846, OM319848; TUB2: OM417078, OM417080; TEF-1α: OM417081, OM417083). BLASTn analyses showed: for ITS and TEF-1α sequences, ≥99.7% identity to the ex-type of G. smithogilvyi (ITS: JQ910642, 474 matching bp; TEF-1α: JQ910645, 335-338 matching bp), and for TUB2 sequences, ≥99.1% identity to G. castaneae (LN999975, 446-453 matching bp). Pathogenicity tests were carried out on surface disinfected nuts of Castanea sativa `Raigona´. A superficial wound was made in the pericarp of each nut. A 2-mm mycelial plug of a 7-days-old culture of G. smithogilvyiwas then inoculated: twenty nuts with isolate EFA924A and twenty with isolate EFA962.4A. Twenty nuts inoculated with sterile agar were used as control. The holes were sealed with Parafilm®. Nuts were incubated in a moist chamber at 22±2°C. Two replicated tests were carried out. Four inoculated and four control nuts were inspected for the presence and progress of rot symptoms every seven days. Three weeks after inoculation, all remaining inoculated nuts were completely rotted, whereas all control nuts remained healthy. Gnomoniopsis smitholgilvyi was reisolated from all inoculated nuts, and it was not recovered from the controls. This pathogen causes chestnut brown rot on sweet chestnut worldwide (EPPO, 2022), causing also shoot cankers on chestnut (Lione et al, 2019). This is the first report of G. smithogilvyi causing chestnut brown rot on nuts and burrs of C. sativa in Spain. Future studies on the incidence of this pathogen and its impact on chestnut yield should be carried out in the main European producing countries, i.e. Spain, Italy, Portugal and Greece, where the disease has been detected and represents an emerging threat to chestnut production.

Straw Competition and Wheat Root Endophytism of Trichoderma gamsii T6085 as Useful Traits in the Biological Control of Fusarium Head Blight.

Trichoderma gamsii T6085 has been investigated for many years as a beneficial isolate for use in the biocontrol of Fusarium head blight (FHB) of wheat caused primarily by Fusarium graminearum. Previous work focused on application of T6085 to wheat spikes at anthesis, whereas application to soil before or at sowing has received limited attention. In the present study, the competitive ability of T6085 on plant residues against F. graminearum was investigated. Results showed a significant reduction of wheat straw colonization by the pathogen and of the development of perithecia, not only when T6085 was applied alone but also in the presence of a F. oxysporum isolate (7121), well known as a natural competitor on wheat plant residues. T6085 was able to endophytically colonize wheat roots, resulting in internal colonization of the radical cortex area, without reaching the vascular system, as confirmed by confocal microscopy. This intimate interaction with the plant resulted in a significant increase of the expression of the plant defense-related genes PAL1 and PR1. Taken together, competitive ability, endophytic behavior, and host resistance induction represent three important traits that can be of great use in the application of T6085 against FHB not only on spikes at anthesis but potentially also in soil before or at sowing.

High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome.

BACKGROUND: Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. METHODS: From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. RESULTS: In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 - 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 - 6.9) and 42.0 % (95 %CI 32.4 - 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 - 3.33, P  = 0.04 and OR 2.62, 95 %CI 1.18 - 5.81, P  = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. CONCLUSIONS: Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

Is Exploitation Competition Involved in a Multitrophic Strategy for the Biocontrol of Fusarium Head Blight?

Trichoderma gamsii T6085 was used in combination with a Fusarium oxysporum isolate (7121) in order to evaluate, in a multitrophic approach, their competitive ability against F. graminearum, one of the main causal agents of Fusarium head blight (FHB) on wheat. The two antagonists and the pathogen were coinoculated on two different natural substrates, wheat and rice kernels. Both T6085 and 7121, alone and coinoculated, significantly reduced the substrate colonization and mycotoxin production by the pathogen. The two antagonists did not affect each other. Using a metabolic approach (Biolog), we investigated whether exploitation competition could explain this antagonistic activity. The aim was to define whether the three fungi coexist or if one isolate nutritionally dominates another. Results obtained from Biolog suggest that no exploitative competition occurs between the antagonists and the pathogen during the colonization of the natural substrates. Interference competition was then preliminarily evaluated to justify the reduction in the pathogen's growth and to better explain mechanisms. A significant reduction of F. graminearum growth was observed when the pathogen grew in the cultural filtrates of T. gamsii T6085, both alone and cocultured with F. oxysporum 7121, thus suggesting the involvement of secondary metabolites. As far as we know, this is the first time that an ecological study has been performed to explain how and which kind of competition could be involved in a multitrophic biocontrol of FHB.

Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study.

OBJECTIVE: Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN: From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS: In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS: Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.

BACKGROUND: The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology. METHODS: Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: A total of 246 miRNAs were differentially expressed (fold change ≥ ± 2, P ≤0.05) between OA and non-OA BM-MSC samples; these miRNAs showed variable interactions depending on the cell and differentiation status. Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis. In particular hsa-miR-335-5p, a critical regulator in bone homeostasis, was further studied. hsa-miR-335-5p downregulation in OA-MSCs, as well as their host coding gene, MEST, were also assessed. CONCLUSIONS: To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation. We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features. These findings, may contribute to our understanding of the molecular mechanisms involved in MSCs mediated homeostatic control in OA pathophysiology that could be applicable in future therapeutic approaches.

Ischemic etiopathogenesis as the possible origin of post-double baloon enteroscopy pancreatitis. A porcine model study.

The aim is to evaluate the pancreatic vascular-ischemic effects related to double balloon enteroscopy in the porcine model as a possible etiopathogenesis of post-enteroscopic pancreatitis. For this reason we carry out two independent experiments in a porcine animal model. In the first arm protocol (group I), 10 animals underwent 90 minutes of oral enteroscopy with 7 days follow-up.The levels of amylase, lipase and C-reactive protein were measured at T0 basal-T1 -90 min, T2-24, T3-7 days. Also we perform upper gastrointestinal endoscopy in a control group. At 7 days, the animals of experimental protocol-I had their pancreases removed for a pathological and immunohistochemical study to evaluate vascular epithelial growth factor (VEGF) expression.The second experimental protocol in this study aims to evaluate possible changes in vascular topography due to the double balloon enteroscopy (DBE). Group-II (10 animals) underwent oral enteroscopy and selective angiography of the cranial mesenteric artery and celiac trunk. None of the group I or control group animals presented pancreatitis, although the biochemical results for group-I showed increases in the levels of amylase, lipase and C reactive protein at 24 hours. The microscopic study for group-I showed pancreatic necrotic foci and positive VEGF expression, though these changes were not expressed in the control group.These foci were found in 50% of the group I animals and in relation to the total of the parenchyma were quantified at 6% of the pancreas. The results for group-II showed that the enteroscopy caused mobilization of the mesenteric vascular axis, with signs of both intestinal and pancreatic hypoperfusion. The conclusions of this study are that, after enteroscopy in the porcine model, pancreatic necrotic foci are produced, in addition to ischemic phenomena causing VEGF expression. This could be related to episodes of visceral hypoperfusion caused by vascular alterations on a topographic level. This can be related to the possible ischemic etiopathogenesis described for post-enteroscopic pancreatitis.

Selected reaction monitoring assays in mesenchymal stem cells from osteoarthritis patients.

Osteoarthritis (OA) is considered the most prevalent form of arthritis. The aim of this study was to verify potential protein OA biomarkers by applying Selected Reaction Monitoring (SRM) assays to protein extracts obtained from Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) isolated from OA patients. BM aspirates were obtained from the femoral channel of OA patients at the time of surgery and from the femoral channel of hip fracture subjects without OA during hip joint replacement surgery for the treatment of subcapital fracture. SRM results verified the differential expression of several protein biomarkers in BM-MSCs from OA patients.

Prevalence and characteristics of chronic kidney disease in people with type 2 diabetes mellitus in the Autonomous Community of Aragon.

AIMS: The main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD. METHODS: Observational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed. RESULTS: The prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria. CONCLUSIONS: The prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression.

A comprehensive examination of small-bowel capsule endoscopy in Spanish centers to meet European Society of Gastrointestinal Endoscopy standards.

Background and study aims In 2019, the European Society of Gastrointestinal Endoscopy (ESGE) created a working group to develop technical and quality standards for small-bowel capsule endoscopy (SBCE) to improve the daily practice of endoscopy services. They developed 10 quality parameters, which have yet to be tested in a real-life setting. Our study aimed to evaluate the accomplishment of the quality standards in SBCE established by the ESGE in several Spanish centers. Materials and methods An online survey of 11 multiple-choice questions related to the ESGE performance measures was sent to Spanish centers with experience in SBCE. In order to participate and obtain reliable data, at least 100 questionnaires had to be answered per center because that is the minimum number established by ESGE. Results 20 centers participated in the study, compiling 2049 SBCEs for the analysis. Only one of 10 performance measures (cecal visualization) reached the minimum standard established by the ESGE. In five of 10 performance measures (Indication, lesion detection rate, terminology, and retention rate) the minimum standard was nearly achieved. Conclusions Our study is the first multicenter study regarding SBCE quality performance measures in a real setting. Our results show that the minimum standard is hardly reached in most procedures, which calls into question their clinical applicability in real life. We suggest performing similar studies in other countries to evaluate whether there is a need for quality improvement programs or a need to reevaluate the minimum and target values published so far.

Effect of the SARS-CoV-2 pandemic on colorectal cancer diagnosis and prognosis.

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.

Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis.

OBJECTIVE: To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA). METHOD: RA patients were selected from a group of subjects genotyped for the rs8192284 SNP, located at the proteolytic cleavage site of IL-6R. sIL6R and protease levels (ADAM17) were measured and the contribution of alternative splicing in the generation of sIL-6R was evaluated through qRT-PCR. RESULT: Increased sIL-6R plasma levels and expression of spliced isoform generating sIL-6R are genotype dependent. ADAM17 concentrations were independent of the genotype studied. CONCLUSION: Alternative splicing and proteolytic cleavage participate in sIL-6R generation in RA. The rs8192284 polymorphism determines the sIL-6R plasma level through differential proteolytic rupture controlled by ADAM17.

Carbon dioxide insufflation safety in double-balloon enteroscopy: an experimental animal study.

AIM: The aim of the present study was to assess the safety and efficacy of CO(2) during double-balloon enteroscopy (DBE) in an experimental animal model study. In this study, insufflation with room air and with CO(2) was compared. METHODS: Twenty healthy swines were used. The animals were randomly allocated to two groups. The room air-DBE group was insufflated with room air, whereas the CO(2)-DBE group was insufflated with CO(2). Endoscopy duration was 90 min. The following parameters were measured during the study (basal, 30 min, 60 min, 90 min): invasive hemodynamic parameters, ventilatory parameters, arterial blood gases, exploration depth, as well as biochemical tests. Residual gas was evaluated at the end of DBE, at 180 min and 24 h after DBE. RESULTS: During the endoscopic exploration none of the animals showed hemodynamic, ventilatory or arterial blood gas alterations in the normal reference range for the swine species. The CO(2) group showed statistically significant differences over the room air group with lower post-procedure residual gas and greater depth of the small bowel explored. CONCLUSION: The use of CO(2) for insufflation during DBE was safe and no complications associated with CO(2) were observed. In addition, the use of CO(2) offers benefits over the use of room air for insufflation during DBE.

Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset.

To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO. Genotyping of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 and signal transducers and activators of transcription 4 (STAT4) rs7574865 polymorphism was performed using fast real-time PCR System. Shared epitope, antibodies directed against cyclic citrulinated peptide (anti-CCP) antibodies and a higher level of education were associated with a younger age at disease onset (P = 0.033, P = 0.004 and P < 0.0001, respectively). Neither carriers of the minor allele of PTPN22 rs2476601 nor STAT4 rs7574 polymorphisms showed a significant association with a younger age at disease onset (P = 0.355, P = 0.065, respectively). We found an additive effect of the three genetic markers in the age at onset: subjects with three markers were associated with a disease onset 9.56, 8.61, and 6.41 years before than those with none, one, or two genetic markers (P = 0.004, P = 0.006 and P = 0.043, respectively). We also described the additive effect of shared epitope, anti-CCP antibodies, educational level, PTPN22, and STAT4 polymorphisms in age at onset. Patients with two, three, four, or five variables were associated with a significant younger age of disease onset (4.72 [0.05-9.38] years (P = 0.048), 9.56 [4.72-14.40] years (P < 0.0001), 12.74 [6.84-18.64] years (P < 0.0001), and 20.87 [10.40-37.17] years (P < 0.0001)). Risk factors for the development of rheumatoid arthritis are also associated, with an additive effect, with a younger age at disease onset.

The Fungal Endophyte Penicillium olsonii ML37 Reduces Fusarium Head Blight by Local Induced Resistance in Wheat Spikes.

The fungal endophyte Penicillium olsonii ML37 is a biocontrol agent of Fusarium head blight in wheat (caused by Fusarium graminearum), which has shown a limited direct inhibition of fungal growth in vitro. We used RNA-seq and LC-MS/MS analyses to elucidate metabolic interactions of the three-way system Penicillium-wheat-Fusarium in greenhouse experiments. We demonstrated that P. olsonii ML37 colonises wheat spikes and transiently activates plant defence mechanisms, as pretreated spikes show a faster and stronger expression of the defence metabolism during the first 24 h after pathogen inoculation. This effect was transient and the expression of the same genes was lower in the pathogen-infected spikes than in those infected by P. olsonii alone. This response to the endophyte includes the transcriptional activation of several WRKY transcription factors. This early activation is associated with a reduction in FHB symptoms and significantly lower levels of the F. graminearum metabolites 15-acetyl-DON and culmorin. An increase in the Penicillium-associated metabolite asperphanamate confirms colonisation by the endophyte. Our results suggest that the mode of action used by P. olsonii ML37 is via a local defence activation in wheat spikes, and that this fungus has potential as a novel biological alternative in wheat disease control.

Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity.

Soluble interleukin-6 receptor α subunit (sIL-6R) is primarily generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A > C) resulting in an aspartic acid to alanine substitution (D358A) at the proteolytic cleavage site. The aim of this study was to determine whether plasma levels of sIL6R are influenced by the rs8192284 polymorphism in patients with rheumatoid arthritis and to assess the association between plasma sIL-6R levels and disease activity as reflected by anti-CCP status. Thirty-nine patients were randomly selected from a cohort of patients with RA of Spanish descent. Plasma sIL-6R concentrations were measured using sandwich ELISA. Genotyping of the rs8192284 (A > C) polymorphism was done using a Fast Real-Time PCR System. DAS 28 scores were used to assess disease activity. Plasma sIL-6R levels were positively associated with the number of C alleles (AA: 35.27 (3.50) ng/ml, AC: 45.50 (4.58) ng/ml, CC: 52.55 (3.18) ng/ml, P = 0.0001). DAS28 and plasma sIL-6R levels were positively associated in the anti-CCP-positive subgroup (r (2) = 0.45, P = 0.0336) and negatively associated in the anti-CCP-negative subgroup (r (2) = -0.45, P = 0.0825). No association between anti-CCP status and sIL-6R level was found. Our findings show that the rs8192284 polymorphism is operative in patients with RA. The presence of anti-CCP antibodies determines the relationship between sIL-6R concentration and disease activity.

[Present and future of the approach to frailty within the health promotion and prevention strategy's framework in the National Health System.] / Presente y futuro del abordaje de la fragilidad en el marco de la estrategia de promoción de la salud y prevención en el Sistema Nacional de Salud.

Our country has achieved one of the highest life expectancies in the world, but this increase has not been matched by a similar growth in healthy life years. Maintaining people's functional capacity as they grow older is essential to provide quality of life for the years they have gained, acting on factors that are modifiable and therefore subject to intervention, such as frailty. This is why it was one of the prioritised interventions in the Prevention and Health Promotion Strategy of the Spanish NHS, which began in 2013. In the collective effort to meet the challenge of addressing frailty, the Autonomous Communities and Cities (AACC) have played a key role in implementing actions on the prevention of frailty and falls in the elderly. The 2019 evaluation of the 3 Consensus document on frailty and falls prevention among the elderly showed very positive data, with high or very high implementation in the AACC. The COVID-19 pandemic has also conditioned the approach to frailty. Frailty has been shown to be a risk factor for the development of illness and death, while COVID-19 has been shown to be a frailty generator. To facilitate the care of the elderly and the approach to frailty, the Ministry of Health, within the EPSP Frailty and Falls Working Group, developed the document of Recommendations for the approach to frailty in the health crisis situation generated by the COVID-19. The future of the approach to frailty in the EPSP is set out in the Roadmap for Addressing Frailty, developed in the framework of the EPSP and the ADVANTAGE Joint Action, which aims to contribute to making frailty a public health priority and to promote its approach at population and individual level, including prevention, early population detection and surveillance/monitoring, from an integrated and coordinated model of care, without forgetting the strengthening of training and research. In the current situation of tension in the socio-health system, which has manifested itself since the COVID-19 crisis, it is necessary to articulate how to continue to provide quality care, not only for the acute situation, but also for other situations such as frailty, care for chronic diseases, geriatric syndromes and physical, mental and social needs. A disability-free life expectancy must be based on the promotion of active and healthy ageing to ensure that older people maintain maximum functional capacity. To this end, it is essential to assess and prevent or reverse frailty, avoiding progression to disability and further overburdening of the system, individuals, families and society as a whole.

Nuestro país ha alcanzado una de las esperanzas de vida más altas del mundo, pero este incremento no se ha acompañado de un crecimiento similar en años de vida en buena salud. Para dotar de calidad de vida los años ganados, es fundamental mantener la capacidad funcional de las personas a medida que envejecen, actuando en factores que son modificables y, por tanto, sujetos a intervención, como la fragilidad. Por ello, ésta fue una de las intervenciones priorizadas en la Estrategia de Promoción de la Salud y Prevención en el SNS (EPSP), que comenzó en el año 2013. En el esfuerzo colectivo por afrontar el reto del abordaje de la fragilidad, las comunidades y ciudades autónomas (CCAA) han tenido un papel fundamental en la implementación de acciones sobre la prevención de la fragilidad y caídas en la persona mayor. La evaluación de 2019 del Documento de consenso sobre prevención de fragilidad y caídas en la persona mayor, arrojó datos muy positivos, con una implementación alta o muy alta en las CCAA. La pandemia de COVID-19, ha condicionado también el abordaje de la fragilidad. Ésta se ha mostrado como un factor de riesgo para el desarrollo de enfermedad y fallecimiento, a la vez que la COVID-19 se ha manifestado como una enfermedad fragilizante. Para facilitar la atención de las personas mayores y el abordaje de la fragilidad desde el Ministerio de Sanidad, en el seno del Grupo de Trabajo de Fragilidad 2 y Caídas de la EPSP, se desarrolló el documento de Recomendaciones para el abordaje de la fragilidad en situación de crisis sanitaria generada por la COVID-19. El futuro del abordaje de la fragilidad en la EPSP está recogido en la Hoja de Ruta para el abordaje de la Fragilidad, elaborada en el marco de la EPSP y de la Acción Conjunta ADVANTAGE, mediante la que se propone contribuir a convertir la fragilidad en una prioridad de salud pública y a promocionar su abordaje a nivel poblacional e individual, incluyendo su prevención, detección precoz poblacional y vigilancia/monitorización, desde un modelo integrado y coordinado de cuidado, sin olvidar el fortalecimiento de la formación e investigación. En la situación actual de tensión del sistema socio-sanitario, que se ha manifestado a partir de la crisis por la COVID-19, es necesario articular cómo continuar prestando una atención de calidad, no solo a la situación aguda, sino también a otras situaciones como la fragilidad, la atención de las enfermedades crónicas, síndromes geriátricos y a las necesidades físicas, mentales y sociales. Una expectativa de vida libre de discapacidad debe basarse en la promoción de un envejecimiento activo y saludable que garantice que las personas mayores mantengan la máxima capacidad funcional. Para ello es fundamental evaluar y prevenir o revertir la fragilidad, evitando la progresión hacia la discapacidad y la mayor sobrecarga del sistema, las personas, familias y la sociedad en su conjunto.

[Innovating in public health: monitoring of social determinants of health and reduction of health inequities: a priority for Spanish presidency of the European union in 2010]. / Innovando en salud pública: monitorización de los determinantes sociales de la salud y reducción de las desigualdades en salud: Una prioridad para la presidencia española de la Unión Europea en 2010.

Tackling health inequalities to achieve health equity is currently one of the main challenges for developed and developing countries. Aware of this reality, and knowing how relevant for economic and social growth the inequalities in health are, the Spanish Ministry of Health and Social Policy has established "Innovation in Public Health: monitoring social determinants of health and reduction of health inequalities" as one of the priorities for the Spanish presidency of the European Union in the first semester of 2010. Furthermore, a national strategy to tackle health inequalities is being developed in the current political term. By choosing this priority, the Spanish Ministry of Health an Social Policy aims to contribute to move forward a coherent and effective agenda at both European and national level, in a new world stage more aware of the social and economic expenditure of inequity in health and its repercussions on countries welfare and development.

Gastric perforation during removal of an intragastric balloon.

The intragastric balloon system is licensed for temporary use in moderately obese patients who have significant health risks related to their obesity and have failed to achieve and maintain significant weight loss with a supervised weight control program alone. Although intragastric balloons are advocated as safe devices, major complications have been described. We report a case of a gastric perforation during the removal of an intragastric balloon. This is the first case reported in the literature.