Comparing Alzheimer’s and Parkinson’s diseases networks using graph communities structure

Background: Recent advances in large datasets analysis offer new insights to modern biology allowing system-level investigation of pathologies. Here we describe a novel computational method that exploits the ever-growing amount of "omics" data to shed light on Alzheimer's and Parkinson's diseases. Neurological disorders exhibit a huge number of molecular alterations due to a complex interplay between genetic and environmental factors. Classical reductionist approaches are focused on a few elements, providing a narrow overview of the etiopathogenic complexity of multifactorial diseases. On the other hand, high-throughput technologies allow the evaluation of many components of biological systems and their behaviors. Analysis of Parkinson's Disease (PD) and Alzheimer's Disease (AD) from a network perspective can highlight proteins or pathways common but differently represented that can be discriminating between the two pathological conditions, thus highlight similarities and differences. Results: In this work we propose a strategy that exploits network community structure identified with a state-of-the-art network community discovery algorithm called InfoMap, which takes advantage of information theory principles. We used two similarity measurements to quantify functional and topological similarities between the two pathologies. We built a Similarity Matrix to highlight similar communities and we analyzed statistically significant GO terms found in clustered areas of the matrix and in network communities. Our strategy allowed us to identify common known and unknown processes including DNA repair, RNA metabolism and glucose metabolism not detected with simple GO enrichment analysis. In particular, we were able to capture the connection between mitochondrial dysfunction and metabolism (glucose and glutamate/glutamine). Conclusions: This approach allows the identification of communities present in both pathologies which highlight common biological processes. Conversely, the identification of communities without any counterpart can be used to investigate processes that are characteristic of only one of the two pathologies. In general, the same strategy can be applied to compare any pair of biological networks

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

BACKGROUND: Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen's kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. CONCLUSIONS: The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants

COVID-19-Associated Multisystem Inflammatory Syndrome in Children and Cardiovascular Autonomic Control: A Prospective Cohort Study Nine Months after SARS-CoV-2 Infection

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 +/- 2.6 years, m +/- SD) 9 months after acute infection and 18 age- (12.5 +/- 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 +/- 6.4% in controls, 2.5 +/- 3.9% in MIS-C; RMSSD: 34 +/- 19 ms in controls, 21 +/- 14 ms in MIS-C, p < 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 +/- 1.2 mmHg(2) in controls, 1.8 +/- 1.2 mmHg(2) in MIS-C, p < 0.05). The MIS-C group also showed lower diastolic pressure-time indices (DPTI) and systolic pressure-time indices (SPTI), particularly in standing (DPTI: 36.2 +/- 9.4 mmHgs in controls, 29.4 +/- 6.2 mmHgs in MIS-C; SPTI: 26.5 +/- 4.3 mmHgs in controls, 23.9 +/- 2.4 mmHgs in MIS-C, p < 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols

The VENERE study: EffectiVenEss of a rehabilitation treatment with Nordic walking in obEse or oveRweight diabetic patiEnts with cardiovascular disease

Background. Nordic walking (NW) has several potential benefits for individuals with cardiovascular disease (CV), type 2 diabetes, and obesity/overweight. It improves cardiovascular health, including exercise capacity and blood pressure control. It enhances glycemic control and insulin sensitivity in diabetes. It aids in weight management and body composition improvement. NW offers additional advantages such as improved muscular strength, joint mobility, physical activity levels, and psychological well-being. Methods. This open-label study with three arms will aim to evaluate the efficacy, safety, and adherence to exercise prescription in obese/overweight diabetic patients with CV complications. The primary objective will be to assess the CV performance of participants after a 6- and 12-month follow-up period, following a 3-month NW intervention, compared with standard rehabilitation (SR) and cardiological counseling (control group, CG) training lasting 3 months. Results. The results of the study will provide valuable insights into the comparative effectiveness of a NW intervention versus SR and CG training in improving cardiovascular performance in obese/overweight diabetic patients with CV complications. Additionally, safety and adherence data will help inform the feasibility and sustainability of the exercise prescription over an extended period. Conclusions. These findings may have implications for the development of tailored exercise programs for this specific patient population, with the aim of optimizing cardiovascular health outcomes. This protocol was registered on ClinicalTrials.gov with reference ID: NCT05987410 on 10 August 2023

Surface water dissolved aluminum and titanium: Tracers for specific time scales of dust deposition to the Atlantic?

Surface water distributions of dissolved Al (dAl) and dissolved Ti (dTi) were investigated along a meridional Atlantic transect and related to dust deposition estimates. In the zone of Saharan dust deposition, highest dAl concentrations occurred in the tropical salinity minimum and suggest increasing Al dissolution from Saharan aerosols with wet deposition. By contrast, the dTi distribution is not related to precipitation but agrees with the pattern of annual dust deposition. In the zone of Patagonian dust deposition, elevated dTi concentrations contrasted with decreased dAl concentrations, indicating excess dAl scavenging onto biogenic particles in surface waters. Estimated residence times range from months to years for dAl and are ∼10 times higher for dTi. This suggests that dAl reflects seasonal changes in dust deposition, while dTi is related to longer temporal scales. However, spatial variations in input and removal processes complicate the quantification of dust deposition from surface water concentrations

822 Local radiotherapy synergizes with tumor-specific TCR redirected T cells in the rejection of prostate cancer

Background Adoptive T cell therapy (ACT) has become a promising option for cancer patients. While tumor-infiltrating lymphocytes were initially exploited as a source of tumor reactive lymphocytes, T cells genetically redirected to the tumor by TCR/CAR gene transfer are now in clinical validation. In the case of solid tumors, unfavorable immunosuppressive microenvironments remain recognized barriers to therapeutic efficacy. We have recently reported that the therapeutic activity of ACT against poorly immunogenic and indolent prostate cancer is improved by the concurrent targeting of the tumor stroma by mean of T cells redirected to an ubiquitously expressed minor histocompatibility antigen or a tumor vessel targeted TNF derivative. We have now taken the concept further and hypothesized that local radiotherapy (RT), might also synergize with ACT by promoting lymphocyte endothelial transmigration and tumor recognition, and ultimately favor abscopal effects. Methods We investigated the combination of local RT and ACT in TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mice and in mice bearing subcutaneous B16/B16-OVA (MO4) or TRAMP-C2/TRAMP-C2-OVA tumors. Local RT was delivered by X-RAD SmART (the Small Animal Radiation Therapy) microirradiator in single dose or hypo-fractioned regimens. ACT consisted of T cells engineered with tumor-specific TCRs. Immunogenic consequences were analyzed by Real-Time PCR, and flow cytometry (FACS) analyses. Prostate tumor debulking was evaluated by histological analyses. Results We found that local hypofractionated RT and ACT, while individually inefficacious in controlling tumor growth, concurred to the debulking of advanced prostate adenocarcinoma when used in combination in treating TRAMP mice. Mechanistically, exposing isolated tumor cells, or the TRAMP mouse prostate to hypo-fractionated RT regimens induced stronger type-I interferon (IFN-I) responses, when compared to single high dose. Acutely, hypofractionated RT promoted better immune tumor infiltration, among which TCR redirected effector cells. Conclusions Data support feasibility and efficacy of combining hypo-fractionated local RT with ACT in the form of TCR engineered T cells to promote prostate cancer recognition and eradication. Tumor debulking was observed in the absence of treatment-related toxicity. Systemic recirculation of TCR redirected T cells was observed. We are now investigating therapeutic effects at distal (metastatic) sites. Acknowledgements The authors acknowledge the support of the Italian Association for Cancer Research (AIRC) Ethics Approval The studies involving animals were approved by The Institutional Ethical Committee (IACUC#999)

The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica)

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51 kya, into the Americas, from where a relatively recent (<20 kya) back migration to Asia took place. The exception to the haplogroup subspecies specificity is represented by the sedentary Levantine H. r. transitiva that extensively shares haplogroup A with the migratory European H. r. rustica and, to a lesser extent, haplogroup B with the Egyptian H. r. savignii. Our data indicate that rustica and transitiva most likely derive from a sedentary Levantine population source that split at the end of the Younger Dryas (YD) (11.7 kya). Since then, however, transitiva received genetic inputs from and admixed with both the closely related rustica and the adjacent savignii. Demographic analyses confirm this species' strong link with climate fluctuations and human activities making it an excellent indicator for monitoring and assessing the impact of current global changes on wildlife

Updates on radiotherapy-immunotherapy combinations: Proceedings of 6(th) annual ImmunoRad conference

Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference

Thermographic imaging in sports and exercise medicine: a Delphi study and consensus statement on the measurement of human skin temperature

The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n = 24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique