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Background The goal of this study was to investigate the prevalence and factors associated with persistent viral shedding (PVS) in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods This was a prospective observational study including all consecutive adults hospitalized with SARS-CoV-2 infection. When the first nasopharyngeal swab was positive for SARS-CoV-2 RNA (day 0), additional samples were obtained on days + 3, + 5, + 7 and then once every 7 days until virus detection was negative. PVS was defined as the duration of shedding of at least 21 days after diagnosis. The primary endpoint of this study was the prevalence of PVS. Results Data were obtained regarding 121 consecutive hospitalized patients with SARS-CoV-2 infection (median age 66 years, male sex 65.3%). Overall, the prevalence of PVS was 38% (46/121 patients). According to univariate analysis, factors associated with PVS were immunosuppression (6.7% vs 21.7%, p = 0.02), increased interleukin-6 (IL-6) levels (≥ 35 ng/ml) at the time of diagnosis (43.4% vs 67.3%, p = 0.02), time from onset of symptoms to diagnosis (median days 7.0 vs 3.5, p = 0.001), intensive care unit admission (22.7% vs 43.5%, p = 0.02), and need for invasive mechanical ventilation (20.0% vs 41.3%, p = 0.01). The multivariate analysis indicated that immunosuppression, increased IL-6 levels at the time of diagnosis, time from onset of symptoms to diagnosis, and need for mechanical ventilation were independent factors associated with PVS. Conclusions PVS was detected in up to 38% of hospitalized patients with SARS-CoV-2 infection and was strongly associated with immunosuppression, increased IL-6 levels, and the need for mechanical ventilation. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-020-00381-8.

BACKGROUND Increases in cardiac troponin (cTn) in coronavirus disease 2019 (COVID-19) have been associated with worse prognosis. Nonetheless, data about the significance of cTn in elderly subjects with COVID-19 are lacking. METHODS From a registry of consecutive patients with COVID-19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020, we selected those ≥ 60 year-old and with cTnI measured within three days from the molecular diagnosis of SARS-CoV-2 infection. When available, a second cTnI value within 48 h was also extracted. The relationship between increased cTnI and all-cause in-hospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three knots. RESULTS Of 343 included patients (median age: 75.0 (68.0−83.0) years, 34.7% men), 88 (25.7%) had cTnI above the upper-reference limit (0.046 µg/L). Patients with increased cTnI had more comorbidities, greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal cTnI. Furthermore, they died more (73.9%vs. 37.3%, P < 0.001) over 15 (6−25) days of hospitalization. The association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model (HR = 1.61, 95%CI: 1.06−2.52, P = 0.039) and was linear until 0.3 µg/L, with a subsequent plateau. Of 191 (55.7%) patients with a second cTnI measurement, 49 (25.7%) had an increasing trend, which was not associated with mortality (univariate HR = 1.39, 95%CI: 0.87−2.22, P = 0.265). CONCLUSIONS In elderly COVID-19 patients, an initial increase in cTn is common and predicts a higher risk of death. Serial cTn testing may not confer additional prognostic information.

OBJECTIVES The aim of this study is to develop a Machine Learning (ML) algorithm for an automatic classification of fetal occiput position at transperineal ultrasound (TPU) during the second stage of labor. METHODS Prospective cohort study including singleton term pregnancies (> 37 weeks of gestation) in the second stage of labor, with the fetus in cephalic presentation. Transabdominal ultrasound was preliminarily performed to assess the actual fetal occiput position, which was labeled as occiput anterior (OA) or non-occiput anterior (non-OA). Subsequently, for each case, one sonographic image of the fetal head was acquired on the axial plane using TPU and archived on a cloud for remote analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern recognition feed-forward neural network was trained on the transperineal images to discriminate between OA and non-OA cases. In the training phase the model tuned its parameters in order to approximate correctly the training data - i.e., the training dataset - in order to correctly assess the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the diagnostic performance of the algorithm was evaluated on unlabeled data, which represented the testing dataset. On this group the ability of the ML algorithm to differentiate the OA from the non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and Precision-Recall Area Under the Curve (PR-AUC) were also calculated to assess the algorithm's performance. The Cohen's kappa (k) was finally added to evaluate the agreement between the algorithm and the gold standard. RESULTS Over a period of 24 months, 1219 women in the second stage of labor were enrolled. They were classified as OA (n=801 or 65.7%) or non-OA (n=418 or 34.3%) on the basis of transabdominal ultrasound. From both the sub-groups (OA and non-OA), 70% of the patients were randomly assigned to the training dataset (824 patients) while the remaining 30% (395 patients) were used as testing dataset. On the latter group the ML based algorithm yielded a correct classification of the fetal occiput position in 90.6% of cases (357 out of 395), including 224 out of 246 OA (91.0%) and of 133 out of 149 non-OA images (89.3%). Moreover, for the evaluation the algorithm's performance we found a F1 -score=88.7% and PR-AUC=85.4%. The algorithm showed a balanced performance in the recognition of both anterior and non-anterior occiput positions. Eventually, the robustness of the proposed algorithm was confirmed by a high agreement with the gold standard method (k = 0.81; p

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches., Author summary This is a detailed study of activating and inhibitory receptors in NK cells of COVID-19 patients when first admitted to the hospital for respiratory insufficiency. NK cells are known to be the first line of defense against invading viruses, and regulate downstream B and T cell responses, including antibody production. We observed intense NK cell activation with decreased functional activity, as well as intense circulation of putative tissue resident CD69+CD103+CXCR6+ NK cells, with a related surge in inflammatory CD34+ precursors from the bone marrow. The findings suggest that there is unprecedented trafficking of NK cells from peripheral tissues, their increased death with recruitment of emergency precursors from the bone marrow, and a relationship with the subsequent course of the disease of the patients. This in turn suggests possible areas of treatment and prevention.

The choice of the technique to enter the peritoneal cavity, during a laparoscopy, depends on a lot of variables which hinder a standardized method and, actually, it appears impossible to show, with certainty, the best method to choose for the first abdominal access in gynecological laparoscopy. The preference for one or another technique depends on the operator experience, school and speciality of the surgeon, laparoscopical upgrading and the work environment; many surgical techniques are not yet used due the limits and fears of some surgeons to change the preference in first access approaching and for the lack of operating versatility by a method or another one. A review of the scientific literature, underlines that the major problems during the first laparoscopical abdominal access are two, vascular and intestinal and their percentage is variable. In this paper we describe the large range of methods for open and closed laparoscopy and for direct access, that permit to perform a first abdominal laparoscopical access, and their major possible problems.

– Aim: To evaluate the incidence of occiput posterior position in labour with and without combined spinal epidural analgesia (CSE) by low dose of sufentanyl and ropivacaine. Material and Methods: This study focused on 132 women subdivided in two groups, patients in spontaneous and in labour analgesia, administered by a low dose CSE by sufentanyl and ropivacaine; all women were evaluated by digital examinations and ultrasound till delivery. All data were collected and analyzed by an independent reviewer. Results: In the second stage, 79 were persis- tent occiput posterior position (POPP) fetuses and 36 were translated from anterior to posterior position (TAPP) fetuses. Specifically, in sponta- neous labour on 25 women in anterior position, there were 17 TAPP and in CSE analgesia on 28 women in anterior, there were 19 in TAPP, with- out significant differences. The number of asyn- clitisms was higher in the POPP group (84%) re- spect to the TAPP group (75%), so as the rate of caesarean section (67% versus 52.7%). Conclusions: The labour with low dose of ropi- vacaine and sufentanyl does not increase the oc- ciput posterior position during fetal descent, lead- ing to a POPP. Finally, since in the occiput anterior presentation labour analgesia significantly length- ens time to delivery, in the occiput posterior posi- tion this is significantly increased, with a pro- longed second stage of labour and reduced time of descent of fetal head in obstetric pelvis.

Acoustic sensing is a viable approach for solving issues related to many applications, namely, biomedical, distance measurements, mechanical, health infrastructure monitoring, etc. It is generally sustainable and of no negative impact on the object under test. The use of acoustic sensing under beamforming technique is an important asset to be exploited, especially for the aforementioned applications. This paper illustrates a generalized approach of modeling and designing a full beamfomer using two specific classes: LCMP (Linear Constrained Minimum Power) beamformers that are used to overcome robustness limitations and MVDR (Minimum Variance Distortionless Response) beamformers. Any aspect of modeling and designing is always related to the DOA (Direction of Arrival). The obtained results are based on assumptions extracted from an actual case of constructed system.

Device performances can be improved by means of nanotcchnology using nanoparticles at certain quantities. AFM (atomic force microscopy) deals with scanning technique to provide on high resolution, 3 D images of sample surfaces. These surfaces included in this paper are related to devices with specific conductivity and must be characterized in terms of metrics, and imaging. The characterization intends to point out spurious nanoparticles that would have been produced during the fabrication process. Spurious particles can change electric resistance, hence conductivity with a huge impact in nanoscale. Imaging is here used to decide if spurious nanoparticles, in terms of quality, arc acceptable or not.

Bio-implantable circuits always raise interest because it is already the frontier of overcoming different deficiencies of human body physiological limitations and impairments. They allow, on one hand the operating mode of internal organs, and the contact with outside, at the other hand, thanks to wired and/or wireless architectures. EEG (Electroencephalogram) signals are an example of a topic where scientists and researchers have been working to use them for preventing general and specific pathologies regarding namely central nervous system and other physiological aspects. This paper illustrates preliminary results of nanocircuits used for a bio-implantable neuro-case encompassing circuits useful for signal processing and measurement.

― Functionalized nanoparticles to be used for drug delivery must undergo specific verifications in accordance to preestablished requirements. Acquiring TEM (transmission electron microscopy) imaging dealing with nanoparticles functionalization, it is possible to encounter possible faults in the shape of the nanoparticles due to surplus of materials or loss in doses of the materials. Even if the functionalizing instrumentation is equipped with dedicated systems acting accordingly, a further “check and balance” process could be useful using for instance imaging. The paper illustrates the application of an optimized and automatic segmentation technique for determining shapes and sizes the aforementioned nanoparticles.

Diagnosis by imaging is one of the most important findings in biomedical imaging because it allows not only the diagnosing of a specific pathology but to perform online and offline surgical operations using imaging as it is noticed in interventional radiology. This paper illustrates the use Hough transform in identifying pathological structures included in CT (Computer Tomography) and HRCT (High Resolution Computer Tomography) images related to patients suffering from lung disease. These abnormal areas appear as bulges of the trophic vessels and they are similar to circular structures with level of lighter gray near to white. Circular Hough transform (CHT) identifies regions with a circular shape. However, a metrics is defined in order to understand if the pointed out area has a pathological morphology. CHT is used here for helping to detect possible events of indolent tumors or undetermined significance pathologies for lung apparatus. For this aim, we use entropy approach with CHT because it measures the scatter of the directional elements in an image. In fact a high entropy value is related to areas with a strong contrast in grayscale, and abnormalities in the image are present as a set of points with more lighter than the dark background. The results have shown, by means of an accuracy true table, rendering a comparison between clinicians’diagnosis and CHT detection, it is possible to indicate, with a better accuracy, potential areas of undetermined significance pathologies. Finally, a receiver operational curve (ROC) is used as an accuracy index for evaluating the positive impact of entropy on diagnosis

Multimodal contrast agents (CAs) allow the enhancement of medical images acquired through different techniques by employing a single contrast injection, with significant benefits for diagnostic outcome. The present study is focused on the characterization of the magnetic behavior of a novel CA class, consisting of silica (Si) nanoparticles (NPs) covered by either superparamagnetic iron oxide (SPIO) NPs or FePt-IO nanocrystals and designed to be detected through both ultrasound and magnetic resonance imaging (MRI). The use multimodal nanoparticles as negative MRI contrast agents could open up new perspectives for the development of novel tools for nanomedicine, combining different non-ionizing techniques for targeted imaging of specific diseased cells. In this work, we simulated the MRI signal of a blood vessel in presence of the new bimodal CAs and compared it with the response of the superparamagnetic NPs alone. The performed numerical simulations showed that the magnetic response of the novel nanocomposites, in terms of signal magnitude, was similar to that of the conventional superparamagnetic NPs for values of echo time (T E ) shorter than 0.4 ms, while for longer T E values it was even better, showing a stronger vessel enhancement leading to an easier detection of the smaller vessels. Therefore, the tested bimodal NPs have the potential for an effective employment as MRI CAs.

The present investigation was aimed to study the uptake of glucose capped silver nanoparticles (AgNPs-G) by human epithelioid cervix carcinoma (HeLa) cells and the nanoparticles effect on cell cycle progression. Cells were exposed to two different amounts (2×103and 2×104NPs/cell) of AgNPs-G (average size 10 nm) for different times (15 and 30 minutes, 1, 3, 6, 12, 18 and 24 hrs). The uptake of AgNPs by HeLa cells was evaluated by using Graphite Furnace-Atomic Absorption Spectrometry (GF -AAS) and Scanning Electron Microscopy-Energy Dispersive X-ray (SEM-EDX) analysis. Cell cycle was investigated by Fluorescence Activated Cell Sorting (FACS) analysis. AgNPs-G were abundantly taken up by HeLa cells within 2 h of treatment and induced cytotoxicity in a NPs amount- and incubation time- dependent manner. The treatment also determined a AgNPs-G concentration- and time-dependent S and G2/M arrest. The possible influence of the cell cycle on cellular uptake of AgNPs-G needs, however, to be further investigated since the dose of internalized nanoparticles in each cell could vary as the cell advances through the cell cycle.