Pre-asthma: a useful concept? A EUFOREA paper. Part 2-late onset eosinophilic asthma.

The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.

Nasal polyp syndrome: a patient-centred term for CRSwNP by EUFOREA.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinus cavities that significantly affects well-being and social function, particularly in young adults and middle-aged populations. CRSwNP is a common health condition in the Western world, with an estimated prevalence of 3%. Despite worldwide evidence-based treatment guidelines such as the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) chronic rhinosinusitis (CRS) pocket guide, a significant number of patients remain undiagnosed and/or uncontrolled with repeated oral corticosteroids (OCS) treatments and/or (multiple) endoscopic sinus surgeries (ESS).

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens.

BACKGROUND: Belatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone. METHODS: The records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B0, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B1, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed. RESULTS: There were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B0: 67.48 vs. B1: 59.10, p = 0.0014). Graft failure at 12 (B0: 1.28% vs. B1: 0.84%, p = 1.0) and 24 months (B0:2.55% vs. B1: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B0: 1.27% vs. B1: 2.52%, p = 0.408) or 24 months (B0: 2.12% vs. B1: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia. CONCLUSION: Non-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1-allergic asthma.

Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.

Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance.

BACKGROUND: Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. RESULTS: In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. CONCLUSIONS: This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

BACKGROUND: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. OBJECTIVE: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (n = 200) within these populations. METHODS: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. RESULTS: We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene-environment or gene-gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. CONCLUSION: These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.

Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous.

Folate-dependent one-carbon cycle metabolism (FOCM) plays a critical role in maintaining genomic stability through regulating DNA biosynthesis, repair and methylation. Folate metabolites as well as other metabolites in the FOCM are hypothesized to be altered when cells transition from normal to cancerous state. Using cells at different stages in their development into colorectal cancer, the FOCM metabolites were profiled as an effort to phenotype the cells, and the metabolite levels were compared to the expressions of related genes. Here, we investigate whether there is a correlation between the metabolite levels, DNA methylation levels and the expression of the related genes that drive the levels of these metabolites. Using CRL1459, APC10.1, HCT116 and Caco-2, we show for the first time that FOCM metabolites correlate with the gene expression patterns. These differences follow a trend that may facilitate distinguishing colon cells at the different stages as they transition into cancerous state. The folate distribution and methionine levels were found to be key in determining the staging of the colon cells in CRC development. Also, expression of CBS, MTRR and MAT genes may facilitate distinguishing between untransformed and transformed colon cells.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Extended memory lifetime in spiking neural networks employing memristive synapses with nonlinear conductance dynamics.

Spiking neural networks (SNNs) employing memristive synapses are capable of life-long online learning. Because of their ability to process and classify large amounts of data in real-time using compact and low-power electronic systems, they promise a substantial technology breakthrough. However, the critical issue that memristor-based SNNs have to face is the fundamental limitation in their memory capacity due to finite resolution of the synaptic elements, which leads to the replacement of old memories with new ones and to a finite memory lifetime. In this study we demonstrate that the nonlinear conductance dynamics of memristive devices can be exploited to improve the memory lifetime of a network. The network is simulated on the basis of a spiking neuron model of mixed-signal digital-analogue sub-threshold neuromorphic CMOS circuits, and on memristive synapse models derived from the experimental nonlinear conductance dynamics of resistive memory devices when stimulated by trains of identical pulses. The network learning circuits implement a spike-based plasticity rule compatible with both spike-timing and rate-based learning rules. In order to get an insight on the memory lifetime of the network, we analyse the learning dynamics in the context of a classical benchmark of neural network learning, that is hand-written digit classification. In the proposed architecture, the memory lifetime and the performance of the network are improved for memristive synapses with nonlinear dynamics with respect to linear synapses with similar resolution. These results demonstrate the importance of following holistic approaches that combine the study of theoretical learning models with the development of neuromorphic CMOS SNNs with memristive devices used to implement life-long on-chip learning.

Resistive switching in sub-micrometric ZnO polycrystalline films.

Resistive switching (RS) devices are considered as the most promising alternative to conventional random access memories. They interestingly offer effective properties in terms of device scalability, low power-consumption, fast read/write operations, high endurance and state retention. Moreover, neuromorphic circuits and synapse-like devices are envisaged with RS modeled as memristors, opening the route toward beyond-Von Neumann computing architectures and intelligent systems. This work investigates how the RS properties of zinc oxide thin films are related to both sputtering deposition process and device configuration, i.e. valence change memory and electrochemical metallization memory (ECM). Different devices, with an oxide thickness ranging from 50-250 nm, are fabricated and deeply characterized. The electrical characterization evidences that, differently from typical nanoscale amorphous oxides employed for resistive RAMs (HfO x , WO x , etc), sub-micrometric thicknesses of polycrystalline ZnO layers with ECM configuration are needed to achieve the most reliable devices. The obtained results are deeply discussed, correlating the RS mechanism to material nanostructure.

Anti-vimentin Antibodies Present at the Time of Transplantation May Predict Early Development of Interstitial Fibrosis/Tubular Atrophy.

BACKGROUND: Anti-vimentin (a cytoskeletal protein) autoantibodies in renal transplant recipients have been correlated with interstitial fibrosis/tubular atrophy (IFTA). In this study, we examine the association between pretransplantation anti-vimentin antibodies and the subsequent development of IFTA. METHODS: Sera obtained before renal transplantation from 97 transplant recipients were analyzed for the presence of anti-vimentin antibodies via Luminex assays to determine the concentration of anti-vimentin antibodies. Results were correlated with findings of IFTA on biopsy as well as graft function and patient and graft survival. RESULTS: In our patient population, 56 of 97 patients were diagnosed by biopsy with IFTA 2.9 (±2.1) years after renal transplantation. Patients with IFTA on biopsy had higher mean concentration of anti-vimentin antibodies when compared to patients without IFTA (32.2 µg/mL [3.97-269.12 µg/mL] vs 14.57 µg/mL [4.71-87.81 µg/mL]). The risk of developing IFTA with a concentration of anti-vimentin antibody >15 µg/mL before transplantation was 1.96 (95% CI = 1.38-2.79, P = .011). Patients with elevated anti-vimentin antibody concentrations (>15 µg/mL) at the time of transplantation also had a higher risk of developing IFTA (81.4% vs 41.2%; P < .05). In addition, graft function was worse at 1, 3, and 5 years posttransplantation in patients with elevated concentrations of pretransplantation anti-vimentin antibody. Although there were more graft losses in the IFTA groups (49.12% vs 25.64%, P = .021) and the IFTA patients loss their grafts earlier (4.3 years vs 3.6 years), there was no statistical difference in graft loss rates. CONCLUSIONS: Pretransplantation anti-vimentin antibody concentrations >15 µg/mL may be a risk factor for IFTA.

HLA-A2 reactive antibodies in a patient who types as HLA-A2: The importance of high resolution typing and epitope-based antibody analysis.

This report describes a case of a highly sensitized patient who had serum antibodies reacting with HLA-A2 but whose phenotype included HLA-A2. The determination of HLA mismatch acceptability at the antigen level was problematic, but high-resolution HLA typing information and epitope-based antibody specificity analysis based on the nonself-self paradigm of HLA epitope immunogenicity have provided a solution. This case supports the concept that HLA typing at the allele level offers a better approach to identifying suitable donors for sensitized patients.

Biologia reprodutiva e ausência de frutificação de Aloe saponaria (Aiton) Haw. (Xanthorrhoeaceae) fora do local de origem / Reproductive biology and absence of fruiting of Aloe saponaria (Aiton) Haw. (Xanthorrhoeaceae) outside its place of origin

RESUMO O gênero Aloe, originário principalmente da África, tem atualmente uma ampla distribuição no mundo. No entanto, são poucas as regiões que têm realizado estudos quanto ao sistema reprodutivo. O objetivo do presente trabalho foi analisar as características e o comportamento reprodutivo de Aloe saponaria em Florianópolis, Santa Catarina. Foram conduzidos estudos sobre sua morfologia e biologia floral, visitantes florais e sistema reprodutivo. Esta espécie apresentou uma inflorescência por planta, com um comprimento de 105 ± 0,1 cm e 267 ± 92,7 flores. A razão pólen/óvulo sugere que a espécie é xenogâmica. O volume e concentração de sólidos solúveis totais do néctar potencial foi 16,6 ± 6,3 μL e 22 ± 2,4 °Brix respectivamente. O néctar instantâneo não apresentou diferenças significativas nos períodos avaliados (9:00h e 15:00h) e o estigma permaneceu receptivo até o segundo dia após a antese. Foram coletados 110 insetos visitantes florais, dos quais 61,8% foram indivíduos de Trigona spinipes. Entretanto, nos testes de polinização não foi observada frutificação efetiva, indicando que a propagação vegetativa é o principal tipo de reprodução usado nessa população. Isto pode estar relacionado a um mecanismo de autoincompatibilidade esporofítica, a anormalidades cromossômicas durante a formação do pólen, as condições climáticas, e a escassa variabilidade genética no local de estudo.

ABSTRACT The Aloe genus, originating mainly from Africa, currently has a wide distribution in the world. However, in few regions studies about the reproductive system have been carried on. The aim e of this study was to analyze the characteristics and reproductive performance of the Aloesaponaria in Florianópolis, Santa Catarina. The morphology, floral biology, flower visitors and the reproductive system were determined. The plants presented an inflorescence per plant, with 105 ± 0,1 cm in length and 267 ± 92.7 flowers. The pollen/ovule ratio suggested that the species is xenogamic. The volume and concentration of total soluble solids in the potential nectar were 16.6 ± 6.3 μL and 22 ± 2.4°Brix, respectively. The instant nectar showed no significant differences between the evaluated periods (9:00h and 15:00h) and the stigma remained receptive until the second day the after anthesis. 110 insects were collected, from which 61.8% were from theTrigona spinipesspecies. However, in the pollination tests the fruit set was not observation, indicating that vegetative propagation is the main type of reproduction used by this population. This may be related to a mechanism of sporophytic self-incompatibility, to chromosomal abnormalities during the formation of pollen, to weather conditions, and to the low genetic variability at the study site.