Combining low-dose CT-based radiomics and metabolomics for early lung cancer screening support

Due to its predominantly asymptomatic or mildly symptomatic progression, lung cancer is often diagnosed in advanced stages, resulting in poorer survival rates for patients. As with other cancers, early detection significantly improves the chances of successful treatment. Early diagnosis can be facilitated through screening programs designed to detect lung tissue tumors when they are still small, typically around 3mm in size. However, the analysis of extensive screening program data is hampered by limited access to medical experts. In this study, we developed a procedure for identifying potential malignant neoplastic lesions within lung parenchyma. The system leverages machine learning (ML) techniques applied to two types of measurements: low-dose Computed Tomography-based radiomics and metabolomics. Using data from two Polish screening programs, two ML algorithms were tested, along with various integration methods, to create a final model that combines both modalities to support lung cancer screening

BRONCO: Automated modelling of the bronchovascular bundle using the Computed Tomography Images

Segmentation of the bronchovascular bundle within the lung parenchyma is a key step for the proper analysis and planning of many pulmonary diseases. It might also be considered the preprocessing step when the goal is to segment the nodules from the lung parenchyma. We propose a segmentation pipeline for the bronchovascular bundle based on the Computed Tomography images, returning either binary or labelled masks of vessels and bronchi situated in the lung parenchyma. The method consists of two modules, modeling of the bronchial tree and vessels. The core revolves around a similar pipeline, the determination of the initial perimeter by the GMM method, skeletonization, and hierarchical analysis of the created graph. We tested our method on both low-dose CT and standard-dose CT, with various pathologies, reconstructed with various slice thicknesses, and acquired from various machines. We conclude that the method is invariant with respect to the origin and parameters of the CT series. Our pipeline is best suited for studies with healthy patients, patients with lung nodules, and patients with emphysema

Porphyromonas gingivalis in Alzheimer's disease brains : evidence for disease causation and treatment with small-molecule inhibitors

Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer's disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer's patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1-42, a component of amyloid plaques. Further, gingipains were neurotoxic in vivo and in vitro, exerting detrimental effects on tau, a protein needed for normal neuronal function. To block this neurotoxicity, we designed and synthesized small-molecule inhibitors targeting gingipains. Gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus. These data suggest that gingipain inhibitors could be valuable for treating P. gingivalis brain colonization and neurodegeneration in Alzheimer's disease

Local and systemic evaluation of inflammation in mice model of periodontitis induced by infection with Porphyromonas gingivalis - comparison of two in vivo models

Paradontoza to choroba zapalna wywołana infekcją bakteryjną, charakteryzująca się destrukcją tkanek przyzębia (ubytek kości wyrostka zębodołowego) otaczających ząb, przyczyniająca się do utraty zębów u osób dorosłych. Bakterie Porphyromonas gingivalis, będące głównym czynnikiem etiologicznym zapalenia przyzębia, to gramujemne pałeczki beztlenowe, bytujące w przydziąsłowej płytce nazębnej. Jako, że nadal istnieje potrzeba opracowania zwierzęcego modelu paradontozy, naśladującego tę chorobę u ludzi, celem niniejszej pracy było porównanie skuteczności wywołania paradontozy w dwóch modelach in vivo u myszy, zwanych dalej modelem bezsupełkowym i modelem supełkowym. Oba modele opracowano wykorzystując myszy BALB/c, gdzie ubytek kości wyrostka zębodołowego był indukowany poprzez doustne podawanie 1x109 CFU bakterii P. gingivalis (szczep W83) w okolicę zębów trzonowych. Model supełkowy został wzbogacony o obwiązanie jedwabną nitką drugiego zęba trzonowego górnej szczeki myszy. Zawiesina bakterii podawana była co 48 godziny przez 3 tygodnie, a cały eksperyment trwał 9 tygodni. Porównanie skuteczności obu modeli odbyło się na podstawie oceny zmian fizjologicznych i behawioralnych u myszy, zdolności kolonizacji kieszonek okołozębowych oraz tkanki dziąsła przez bakterie P. gingivalis, poziomu ubytku kości wyrostka zębodołowego w szczęce, zmian histochemicznych i poziomu akumulacji neutrofilii w tkance dziąsła, możliwości migracji bakterii P. gingivalis do narządów wewnętrznych (mózg, płuca, wątroba, śledziona, nerki), poziomu akumulacji neutrofilii w tych narządach, a także ogólnoustrojowej odpowiedzi immunologicznej organizmu poprzez pomiar stężenia cytokin, chemokin pro- i przeciwzapalnych (IL-6, IL-8, IL-10, IL-12p70, IFN-γ, MCP-1) oraz białka C-reaktywnego (CRP) w surowicy z krwi obwodowej.Na podstawie przeprowadzonych badań wykazano (i) brak zmian fizjologicznych i behawioralnych u myszy poza spadkiem masy ciała w obu modelach, (ii) obecność bakterii P. gingivalis zarówno w kieszonkach okołozębowych jak i w tkan¬ce dziąsła w obu modelach, (iii) ubytek kości szczęki na wysokim pozio¬mie w modelu bezsupełkowym i na niskim poziomie w modelu supełkowym, (iv) akumulację licznych komórek zapalnych w obu modelach, (v) obecność bakterii P. gingivalis w narządach wewnętrznych w niższej liczbie w modelu bezsupełkowym i wyższej liczbie w modelu supełkowym, (vi) akumulację komórek zapalnych w narządach wewnętrznych w obu modelach, (vii) brak podwyższenia poziomu cytokin i chemokin w surowicy, (viii) wzrost stężenia białka CRP w surowicy w obu modelach. Na podstawie przedstawionych danych można wysnuć hipotezę, iż lepszym modelem indukującym paradontozę jest model bezsupełkowy z doustną infekcją bakterią P. gingivalis, który wywoływał ubytek kości przyzębia, nie wywołując ogólnoustrojowej odpowiedzi zapalnej ze strony układu immunologicznego.Periodontitis is a polymicrobial oral infection characterized by the destruction of tooth-supporting structures that can be linked to systemic diseases such as cardio-vascular disease, diabetes or rheumatoid arthritis. Porphyromonas gingivalis, as the main pathogen of chronic periodontal disease, is a gram-negative anaerobic bacterium in the subgingival dental plaque. Periodontitis characterizes inflammatory destruction of the alveolar bone and consequently is a major cause of tooth loss in adults. Alveolar bone loss can be induced by ‘oral gavage infection’ or with ligature in mouse model. The first model was established in BALB/c mice, where alveolar bone loss was induced by oral inoculation with 1x109 CFU of live P. gingivalis (W83) suspended in 2% cellulose using a blunt-tipped needle at 2-day intervals by 21 days followed by 42 days were without bacteria inoculation. ‘Ligature model’ was enriched by silk ligature, which is tied around the maxillary left second molar. Comparison of two periodontitis models in vivo was achieved by evaluation of physiological and behavioral changes in mice, the ability to colonize of periodontal/gingiva tissues by P. gingivalis, alveolar bone loss, histochemical analysis and quantification of neutrophils infiltration in gingiva, the ability to disseminate to internal organs (brain, lungs, liver, spleen, kidneys), quantitative analysis of internal organs infiltration by neutrophils (myeloperoxidase assay), and also systemic immunological response by measurement of cytokine (IL-6, IL-8, IL-10, IL-12p70, IFN-γ), chemokine (MCP-1) and C Reactive Protein concentration in serum. Obtained data suggest that in both models of oral infection do not result in significant systemic changes in mice except loss of weight variations. In comparison to the oral gavage model, silk ligatures around second molar caused greater accumulation of P. gingivalis in periodontal pockets. Nevertheless more extensive alveolar bone loss was observed in ‘oral gavage model’. The presence of bacteria in gingiva entails local inflammation. From initial site of infection of the oral cavity P. gingivalis was able to disseminate and colonize internal organs. The colonization correlated with increase of myeloperoxidase activity in infected tissues. Interestingly, both oral infections models did not cause elevation of cytokine and chemokine in blood despite increasing CRP concentration in serum. By all means presented our data suggest that ‘oral gavage model’ is better to imitate periodontitis than the ligature model

Effects of statins on multispecies oral biofilm

Statins effectively reduce the risk of cardiovascular-related morbidity and mortality in patients with hyperlipidemia, hypertension or type-II diabetes. In addition to lowering cholesterol, several studies have attributed statins with immunomodulatory and bactericidal properties. In this context, the aim of this study was to obtain information about their antimicrobial activity against key bacteria populating oral biofilms and relevant in periodontitis. Using the planktonic monocultures and multispecies biofilm models to assess the impact of the four statins here investigated, we demonstrated their high efficacy against Porphyromonas gingivalis (P. gingivalis) also leading to a significant decrease in cumulative bacterial load in early biofilm. Conversely, in established biofilm, simvastatin decreased P. gingivalis counts by up to more than 1ʹ000-fold, but, in contrast with early biofilm, Streptococcus gordonii expanded significantly to populate this emerging niche and compensate for diminishing P. gingivalis counts. These findings allow for speculations that similar events, when occurring in vivo, could initiate a shift of the oral microflora from a pathogenic to a more commensal state. Thus, we believe that simvastatin should be studied as an exemplary drug for periodontitis treatment