Introduction
Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in ...thyroid cells in vitro.
Purpose
Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures.
Methods
Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants.
Results
The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone.
Conclusions
The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.
Adipose tissue is a reservoir of Mesenchymal Stem Cells (Adipose-derived Mesenchymal Stem Cells, ASCs), endowed with regenerative properties. Fat graft was proposed for breast reconstruction in ...post-surgery cancer patients achieving good aesthetic results and tissues regeneration. However, recent findings highlight a potential tumorigenic role that ASCs may have in cancer recurrence, raising some concerns about their safety in clinical application. To address this issue, we established a model where autologous ASCs were combined with primary normal or cancer cells from breast of human donors, in order to evaluate potential effects of their interactions, in vitro and in vivo. Surprisingly, we found that ASCs are not tumorigenic per sè, as they are not able to induce a neoplastic transformation of normal mammary cells, however they could exhacerbate tumorigenic behaviour of c-Met-expressing breast cancer cells, creating an inflammatory microenvironment which sustained tumor growth and angiogenesis. Pharmacological c-Met inhibition showed that a HGF/c-Met crosstalk between ASCs and breast cancer cells enhanced tumor cells migration, acquiring a metastatic signature, and sustained tumor self-renewal. The master role of HGF/c-Met pathway in cancer recurrence was further confirmed by c-Met immunostaining in primary breast cancer from human donors, revealing a strong positivity in patients displaying a recurrent pathology after fat grafts and a weak/moderate staining in patients without signs of recurrence. Altogether our findings, for the first time, suggest c-Met expression, as predictive to evaluate risk of cancer recurrence after autologous fat graft in post-surgery breast cancer patients, increasing the safety of fat graft in clinical application.
Patients suffering from neurological diseases may develop dysarthria, a motor speech disorder affecting the execution of speech. Close and quantitative monitoring of dysarthria evolution is crucial ...for enabling clinicians to promptly implement patients’ management strategies and maximizing effectiveness and efficiency of communication functions in term of restoring, compensating or adjusting. In the clinical assessment of orofacial structures and functions, at rest condition or during speech and non-speech movements, a qualitative evaluation is usually performed, throughout visual observation.
To overcome limitations posed by qualitative assessments, this work presents a store-and-forward self-service telemonitoring system that integrates, within its cloud architecture, a convolutional neural network (CNN) for analyzing video recordings acquired by individuals with dysarthria. This architecture – called facial landmark Mask RCNN – aims at locating facial landmarks as a prior for assessing the orofacial functions related to speech and examining dysarthria evolution in neurological diseases.
When tested on the Toronto NeuroFace dataset, a publicly available annotated dataset of video recordings from patients with amyotrophic lateral sclerosis (ALS) and stroke, the proposed CNN achieved a normalized mean error equal to 1.79 on localizing the facial landmarks. We also tested our system in a real-life scenario on 11 bulbar-onset ALS subjects, obtaining promising outcomes in terms of facial landmark position estimation.
This preliminary study represents a relevant step towards the use of remote tools to support clinicians in monitoring the evolution of dysarthria.
•Quantitative, nonintrusive monitoring of dysarthria is critical to improve care for affected individuals.•Motor speech assessment is essential for monitoring dysarthria evolution.•We propose a store-and-forward self-service telemonitoring system as clinical-decision support system.•The system exploits cloud comping for multimedia data-handling and deep learning for data processing.
To compare the American Thyroid Association (ATA) risk staging of histologically proven papillary thyroid cancer (PTC) in patients who received a presurgery cytologic result of either indeterminate ...thyroid nodules (ITNs, Bethesda III/IV) or suspicious for malignancy/malignant (TIR 4/5, Bethesda V/VI).
Clinical, ultrasonographic, cytological data from patients with histologically diagnosed PTC were retrospectively collected.
Patients were stratified according to the preoperative fine-needle aspiration cytology into 2 groups: 51 ITNs (TIR3A/3B) and 118 suspicious/malignant (TIR 4/5). Male/female ratio, age, and presurgery TSH level were similar between the 2 groups. At ultrasound, TIR 4/5 nodules were significantly more frequently hypoechoic (P = .037), with irregular margins (P = .041), and with microcalcifications (P = .020) and were more frequently classified as high-risk according to the European Thyroid Imaging and Reporting Data System (EU-TIRADS; P = .021). At histology, the follicular PTC subtype was significantly more prevalent among ITNs while classical PTC subtype was more frequent in TIR 4/5 group (P = .002). In TIR 4/5 group, a higher rate of focal vascular invasion (P < .001) and neck lymph node metastasis (P = .028) was observed. Intermediate-risk category according to ATA was significantly more frequent in TIR 4/5 group while low-risk category was more frequently found among ITNs (P = .021), with a higher number of patients receiving radioiodine in TIR 4/5 group (P = .002). At multivariate logistic regression, having a TIR 4/5 cytology was associated with a significant risk of having a higher ATA risk classification as compared to ITN (OR 4.6 95% CI 1.523-14.007, P = .007), independently from presurgery findings (nodule size at ultrasound, sex, age, and EU-TIRADS score).
Papillary thyroid cancers recorded among ITNs are likely less aggressive and are generally assessed as at lower risk according to ATA classification.
BACKGROUND/AIMA native non-pathogenic bacterial microflora was identified in Comano (TN, Italy) spring water. The aim of this study was to investigate the regenerative effects of some of the ...bacterial lysates extracted from this water in a human ex-vivo skin experimental wound model.MATERIALS AND METHODSBacterial lysates were extracted from four new isolates: lysate 1 (L1) - closest relative Rudaea cellulosilytica, phylum Proteobacteria; lysate 2 (L2) - closest relative Mesorhizobium erdmanii, phylum Proteobacteria; lysate 3 (L3) - closest relative Herbiconiux ginseng, phylum Actinobacteria; lysate 4 (L4) - closest relative Fictibacillus phosphorivorans, phylum Firmicutes. Their regenerative effects were investigated in a human ex-vivo skin experimental wound healing model at 3 (T1), 5 (T2), and 10 days (T3).RESULTSThe samples cultured with the L2 lysate displayed both an earlier and complete restoration of all the skin layers and their features were the closest to the normal skin. The regenerated epidermis demonstrated a complete maturation as the normal epidermis. The papillary dermis appeared mature, and the reticular dermis displayed both collagen and elastic fibres regularly parallel to the skin surface. An anti-inflammatory effect was displayed by the L1 lysate, but this action did not constitute a regenerative effect, suggesting that pathways for inflammation and regeneration might be different.CONCLUSIONThe therapeutic power of spring waters is not exclusively related to their mineral composition, but it may also be attributable to their native non-pathogenic bacterial microflora.
The aim of this study was to provide an innovative nomogram to predict the risk of >2 positive nodes in patients fulfilling the Z0011 criteria with 1-2 sentinel lymph nodes (SLNs) only retrieved.From ...2007 to 2017, at the Breast Unit of ICS Maugeri Hospital 271 patients with 1-2 macrometastatic SLNs, fulfilling the Z0011 criteria, underwent axillary dissection and were retrospectively reviewed.A mean of 1.5 SLNs per patient were identified and retrieved. One hundred eighty-seven (69.0%) had 1-2 positive nodes, and 84 (31.0%) had >2 metastatic nodes. Independent predictors of axillary status were: positive SLNs/retrieved SLNs ratio (odds ratio OR 10.95, P = .001), extranodal extension (OR 5.51, P = .0002), and multifocal disease (OR 2.9, P = .003). A nomogram based on these variables was constructed (area under curve after bootstrap = 0.74).The proposed nomogram might select those patients fulfilling the Z0011 criteria, with 1-2 SLNs harvested, in whom a high axillary tumor burden is expected, aiding to guide adjuvant treatments.
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•The composition of microcalcifications in male breast cancer was never studied.•Raman allowed to identify the different mineral components present in a fast way.•Hydroxyapatite was ...detected as the most abundant mineral present.•Raman reveals specific features of microcalcifications in male breast cancer.
Microcalcifications (MCs) are important disease markers for breast cancer. Many studies were conducted on their characterization in female breast cancer (FBC), but no information is available on their composition in male breast cancer (MBC). Raman spectroscopy (RS) is a molecular spectroscopy that can rapidly explore the biochemical composition of MCs without requiring any staining protocol.
In this study, we optimized an algorithm to identify the mineral components present in MCs from Raman images. The algorithm was then used to study and compare MCs identified on breast cancer pieces from male and female patients. In total, we analyzed 41 MCs from 5 invasive MBC patients and 149 MCs from 13 invasive FBC patients.
Results show that hydroxyapatite is the most abundant type of calcium both in MBC and FBC. However, some differences in the amount and distribution of calcium minerals are present between the two groups. Besides, we observed that MCs in MBC have a higher amount of organic material (collagen) than FBC.
To the best of our knowledge, this study provides the first overview of the composition of MCs present in MBC patients; and suggests that these patients have specific features that differentiate them from the previously studied FBC. Our result support thus the need for studies designed explicitly to the understanding of MBC.
The impact of reperfusion therapies on cognition has been poorly explored and little knowledge exists. We explored the influence of endovascular treatment (EVT) on cognitive outcome in patients with ...anterior circulation ischemic stroke. Patients presenting with ischemic stroke due to anterior large vessel occlusion who underwent intravenous thrombolysis (IVT) alone or EVT plus IVT were recruited. Cognitive abilities were evaluated at 6 months from stroke through a neuropsychological test battery. A total of 88 patients with a mean age of 66.3 ± 12.9 years were included, of which 38 treated with IVT alone and 50 with IVT plus EVT. Compared to patients treated with IVT alone, patients who received EVT plus IVT performed significantly better at the neuropsychological tests exploring executive functions, attention, abstract reasoning, visuospatial ability, visual and verbal and memory. At multivariable regression analysis, the EVT was independently associated with the 6-month cognitive performance after the adjustment for age, sex, admission National Institutes of Health Stroke Scale score, systolic blood pressure, glucose level, Alberta Stroke Program Early CT score, side of stroke, site of occlusion, and Back Depression Inventory score Stroop Test Word Reading:
β = 13.99, 95% confidence interval (CI) 8.47-19.50, p < 0.001; Stroop Test Colour Naming:
β = 6.63, 95% CI 2.46-10.81, p = 0.002; Trail Making Test-A:
β = - 92.98, 95% CI - 153.76 to - 32.20, p = 0.003; Trail Making Test-B:
β = - 181.12, 95% CI - 266.09 to - 96.15; p < 0.001; Digit Span Test Forward:
β = 1.44, 95% CI 0.77-2.10, p < 0.001; Digit Span Test Backward:
β = 1.10, 95% CI 0.42-1.77, p = 0.002; Coloured Progressive Matrices:
β = 5.82, 95% CI 2.71-8.93, p < 0.001; Rey Complex Figure Test-Copy:
β = 6.02, 95% CI 2.74-9.30, p < 0.001; Rey Complex Figure Test-Immediate recall:
β = 6.00, 95% CI 2.34-9.66, p = 0.002; Rey Complex Figure Test-Delayed recall:
β = 5.73, 95% CI 1.95-9.51, p = 0.003; Rey Auditory Verbal Learning Test-Immediate recall:
β = 12.60, 95% CI 6.69-18.52, p < 0.001; Rey Auditory Verbal Learning Test-Delayed recall:
β = 1.85, 95% CI 0.24-3.45, p = 0.025. Patients treated with EVT plus IVT had better cognitive performance than patients treated with IVT alone at 6 months from anterior circulation ischemic stroke.
Indeterminate cytological result at fine-needle aspiration cytology (FNAC) remains a clinical challenge for endocrinologists. Aim of the present study was to evaluate whether a coexistent chronic ...autoimmune thyroiditis (CAT) might affect the diagnostic accuracy of fine-needle aspiration cytology for thyroid nodules.
A retrospective cohort study was designed including all nodules receiving an indeterminate cytology result (TIR3A or TIR3B) undergoing thyroid surgery and subsequent histological confirmation. Patients were stratified into two groups according to the presence or absence of CAT. The hypothesis to be tested was whether follicular cell alterations induced by CAT might increase the rate of indeterminate cytological results in histologically benign thyroid nodules. Additional control groups were represented by nodules with determinate cytology, either benign (TIR 2) or malignant (TIR5).
One hundred and eighty-nine indeterminate thyroid nodules were included (67 TIR3A and 122 TIR3B). At post-surgical histology, 46 nodules (24.3%) were malignant. No significant differences were observed in the rate of histologically proven malignancy between patients without CAT and patients with CAT in the TIR3B (29.4% vs 32.4%; P = 0.843) nor TIR3A (13.0% vs 11.4%; P = 1.000) nodules. The rate of coexistent CAT was similar between TIR3B and TIR5 nodules harboring PTC at histology (30.4% vs 39.4%, P = 0.491) and between indeterminate nodules and a control group of TIR2 nodules (39.2% vs 37.0%; P = 0.720).
The similar rates of histologically proven malignancy found in cytologically indeterminate nodules in the presence or absence of concomitant CAT would not support that CAT itself affects the diagnostic accuracy of fine-needle aspiration cytology.
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